Jaguars vs 49ers Prediction — AI Finds CAN'T MISS NFL Lines & Props (Sep 28)
Updated: 2025-09-21T02:28:40.156150ZBy Remi at Leans.AI — AI picks for ATS, ML, OU & props
Jacksonville heads to Levi’s Stadium on September 28, 2025 to take on the unbeaten San Francisco 49ers in what’s shaping up as a high-stakes NFC battle. San Francisco enters as a modest favorite (–3), and the projected total is hovering in the mid-46 to mid-47 range, pointing to expectations of a competitive game with offensive fireworks.
Get key insights, betting trends, and AI-powered predictions to help incorporate into your betting strategies.
GAME INFO
Date: Sep 28, 2025
Start Time: 4:05 PM EST
Venue: Levi's Stadium
49ers Record: (3-0)
Jaguars Record: (2-1)
OPENING ODDS
JAX Moneyline: +143
SF Moneyline: -172
JAX Spread: +3
SF Spread: -3.0
Over/Under: 47
JAX
Betting Trends
- The Jaguars are 1–1 ATS so far this season, with a neutral cover percentage and some upside in matchups where their defense forces turnovers. (Team ATS trends list JAX at 1–1 ATS)
SF
Betting Trends
- San Francisco is 2–0 ATS this season, continuing a trend of covering the spread frequently even in tight games. (Team ATS trends list SF at 2–0 ATS)
MATCHUP TRENDS
- This game is projected to be San Francisco’s highest-scoring yet, with some models projecting 46.5 total points, reflecting the offensive strengths of both teams. Also, public betting is tilting toward the 49ers, especially if Brock Purdy returns to the lineup, which many believe will boost their confidence and efficiency.
JAX vs. SF
Best Prop Bet
- Remi's searched hard and found the best prop for this matchup: T. Lawrence under 230.5 Passing Yards.
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Jacksonville vs San Francisco Prediction & Odds:
Free NFL Betting Insights for 9/28/25
Meanwhile, San Francisco’s defense will aim to do what it does best: disrupt rhythm, collapse the pocket, and force Lawrence into hurried decisions that lead to mistakes, while also clamping down on Jacksonville’s ground game to create long third downs. Special teams could be a hidden factor in this matchup, as both sides are evenly matched on paper and field position swings may prove decisive, particularly in a contest where every possession could matter. From a betting standpoint, the 49ers are favored at –3, having gone 2–0 ATS to start the season, while Jacksonville sits at 1–1 ATS and has been a harder team to predict; early public money has leaned heavily on San Francisco, especially with speculation about Purdy’s return, but the Jaguars’ ability to play spoiler and thrive in underdog spots makes them a live threat if Lawrence is sharp and their defense forces turnovers. The total around 46.5 suggests oddsmakers expect a moderately high-scoring game, and if both quarterbacks find rhythm, this could evolve into a back-and-forth contest where red-zone efficiency and mistake avoidance dictate the outcome. Ultimately, this matchup comes down to adaptability—whether Jacksonville can handle San Francisco’s physicality and execute cleanly on the road, and whether the 49ers can continue to overcome injuries and impose their brand of football. The team that wins the trenches and capitalizes on key opportunities will likely emerge with a victory that strengthens their claim as a legitimate contender in the NFC playoff race.
How good was that?
— Jacksonville Jaguars (@Jaguars) September 23, 2025
@YourSFD | #DUUUVAL
Jacksonville Jaguars NFL Preview
The Jacksonville Jaguars head to Levi’s Stadium on September 28, 2025 eager to prove they can knock off one of the league’s elite and position themselves as true contenders after a solid 2–1 start. Trevor Lawrence remains the centerpiece of the offense, and while he has been sharp in stretches, the Jaguars know they’ll need him at his very best against a San Francisco defense that thrives on creating chaos at the line of scrimmage. Protecting Lawrence will be priority number one, as the Jaguars’ offensive line must hold up long enough to allow him to distribute quickly to his weapons, leaning on intermediate throws, play-action, and tempo to slow down the 49ers’ pass rush. The running game, whether it’s grinding out tough yards between the tackles or creating space on outside zones, must also play a key role in keeping the Niners’ defense honest and giving Lawrence manageable situations on third down. Defensively, Jacksonville faces a tall task, as San Francisco’s balanced offense can attack in multiple ways depending on personnel, and the potential return of Brock Purdy makes them even more dangerous.
The Jaguars’ front seven will have to maintain discipline in their gaps to contain the run, while their secondary must remain sharp against play-action and quick reads that test communication and coverage integrity. Creating turnovers will be critical to flipping field position and keeping the game within striking distance, as the 49ers rarely beat themselves. On special teams, the Jaguars must win hidden yardage battles, as field position could prove decisive in a tight contest where possessions matter more than usual. From a betting perspective, Jacksonville is 1–1 ATS this season, showing mixed results, but as a road underdog in a high-profile spot, they have nothing to lose and could attract contrarian bettors who see value in their young quarterback’s ability to engineer an upset. For the Jaguars, the formula is clear: play clean football, sustain drives with a balanced attack, prevent San Francisco from dictating pace, and strike opportunistically when the chance arises. If they execute with discipline and Lawrence delivers in key moments, Jacksonville could turn what looks like a daunting road test into a statement win that reshapes perceptions of their ceiling in 2025.
Credit: USA TODAY/IMAGN
San Francisco 49ers NFL Preview
The San Francisco 49ers return to Levi’s Stadium on September 28, 2025 with an unbeaten record and the swagger of a team that has shown it can overcome injuries and still impose its will, making them a dangerous opponent for any challenger, including a Jacksonville squad eager to play spoiler. While the absences of stars like George Kittle, Nick Bosa, and Brandon Aiyuk have been obstacles, the 49ers’ depth has been on full display, with backups and role players stepping up to keep the offense efficient and the defense dominant. The potential return of Brock Purdy looms large, as his presence would restore rhythm and aggressiveness to the passing game, giving San Francisco the chance to exploit Jacksonville’s secondary with play-action shots and intermediate precision throws. In the meantime, the run game remains the heartbeat of Kyle Shanahan’s system, with Christian McCaffrey and company capable of dictating tempo, wearing down defenses, and setting up explosive plays in the passing attack.
Defensively, the Niners will look to suffocate Trevor Lawrence by collapsing the pocket, mixing pressure looks, and forcing him into tight throws under duress, while their linebackers and safeties will be tasked with neutralizing Jacksonville’s playmakers in space and eliminating yards after the catch. Special teams also give the 49ers an edge, as their discipline and execution often turn close field-position battles into subtle advantages that add up over four quarters. From a betting perspective, San Francisco’s 2–0 ATS record so far this season highlights their consistency in meeting or exceeding expectations, and with early public money leaning heavily on the Niners at –3, they enter this contest with the market and momentum firmly on their side. Ultimately, San Francisco’s path to victory is built on doing what they do best—running the ball with authority, keeping Purdy or his replacement comfortable with defined reads, and letting their defense dictate terms to a young Jacksonville offense. If they execute their brand of physical, balanced football, the 49ers have every chance not only to stay perfect but to make a statement win at home that reinforces their status as one of the NFC’s most formidable teams.
Big hit McKivitz 💥
— San Francisco 49ers (@49ers) September 24, 2025
Watch the full Mic'd Up powered by @Cisco here: https://t.co/30pKIwCar0 pic.twitter.com/MfziTmfCAC
Jacksonville vs. San Francisco Prop Picks (AI)
Jacksonville vs. San Francisco Prediction (AI)
Remi, our AI sports genius, has been pouring over exorbitant amounts of data from every angle between the Jaguars and 49ers and using recursive machine learning and industry leading AI to boil down the data to a single cover probability.
Oddly enough, we’ve seen the AI has been most keyed in on the unproportionally assigned factor emotional bettors regularly put on player performance factors between a Jaguars team going up against a possibly improved 49ers team. We’ve found the true game analytics appear to reflect a strong lean against one Vegas line specifically.
Unlock this in-depth AI prediction and all of our NFL AI picks for FREE now.
Below is our current AI Jacksonville vs San Francisco picks, computer picks Jaguars vs 49ers, best bets, model edges, confidence ratings.
| DATE | GAME | LEAN | %WIN | UNITS | LEVEL | |
|---|---|---|---|---|---|---|
| ACTIVE PICKS LOCKED - SEE NOW | ||||||
These picks update as information changes—injury reports, weather, and market movement. Each line shows our model’s fair price, the edge versus the market, and a unit confidence rating (1–10). Odds and availability vary by sportsbook and time. Edges are computed against the listed price; value may change after line moves. Always shop for the best number. See the full NFL Schedule.
Jaguars Betting Trends
The Jaguars are 1–1 ATS so far this season, with a neutral cover percentage and some upside in matchups where their defense forces turnovers. (Team ATS trends list JAX at 1–1 ATS)
49ers Betting Trends
San Francisco is 2–0 ATS this season, continuing a trend of covering the spread frequently even in tight games. (Team ATS trends list SF at 2–0 ATS)
Jaguars vs. 49ers Matchup Trends
This game is projected to be San Francisco’s highest-scoring yet, with some models projecting 46.5 total points, reflecting the offensive strengths of both teams. Also, public betting is tilting toward the 49ers, especially if Brock Purdy returns to the lineup, which many believe will boost their confidence and efficiency.
Jacksonville vs. San Francisco Game Info
What time does Jacksonville vs San Francisco start on September 28, 2025?
Jacksonville vs San Francisco starts on September 28, 2025 at 4:05 PM EST.
Where is Jacksonville vs San Francisco being played?
Venue: Levi's Stadium.
What are the opening odds for Jacksonville vs San Francisco?
Spread: San Francisco -3.0
Moneyline: Jacksonville +143, San Francisco -172
Over/Under: 47
What are the records for Jacksonville vs San Francisco?
Jacksonville: (2-1) | San Francisco: (3-0)
What is the AI best bet for Jacksonville vs San Francisco?
Remi's searched hard and found the best prop for this matchup: T. Lawrence under 230.5 Passing Yards.. Prices move—always shop for the best number.
What are Jacksonville vs San Francisco trending bets?
This game is projected to be San Francisco’s highest-scoring yet, with some models projecting 46.5 total points, reflecting the offensive strengths of both teams. Also, public betting is tilting toward the 49ers, especially if Brock Purdy returns to the lineup, which many believe will boost their confidence and efficiency.
What are Jacksonville trending bets?
JAX trend: The Jaguars are 1–1 ATS so far this season, with a neutral cover percentage and some upside in matchups where their defense forces turnovers. (Team ATS trends list JAX at 1–1 ATS)
What are San Francisco trending bets?
SF trend: San Francisco is 2–0 ATS this season, continuing a trend of covering the spread frequently even in tight games. (Team ATS trends list SF at 2–0 ATS)
Where can I find AI Picks for Jacksonville vs San Francisco?
See our latest NFL picks and odds pages for 2025 to compare prices before you bet.
Jacksonville vs. San Francisco Odds
Remi is pouring through loads of stats on each team. In fact, anytime the Jacksonville vs San Francisco trends are analyzed, there’s always several intriguing angles to key in on. Not to mention games played at extreme travel distance can often follow normal, predictable patterns.
Jacksonville vs San Francisco Opening Odds
JAX Moneyline:
+143 SF Moneyline: -172
JAX Spread: +3
SF Spread: -3.0
Over/Under: 47
Jacksonville vs San Francisco Live Odds
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–
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+207
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+5 (-105)
-5 (-115)
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O 45 (-110)
U 45 (-110)
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Nov 2, 2025 1:00PM EST
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O 40 (-110)
U 40 (-110)
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Nov 2, 2025 1:00PM EST
San Francisco 49ers
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49ers
Giants
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–
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-147
+127
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-2.5 (-115)
+2.5 (-105)
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O 49 (-103)
U 49 (-117)
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Nov 2, 2025 1:00PM EST
Los Angeles Chargers
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Chargers
Titans
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-500
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-9.5 (-105)
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O 43.5 (-108)
U 43.5 (-112)
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Nov 2, 2025 1:00PM EST
Minnesota Vikings
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11/2/25 1PM
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Lions
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–
–
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+374
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+9 (-110)
-9 (-110)
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O 47.5 (-117)
U 47.5 (-103)
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–
–
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+754
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+13.5 (+100)
-13.5 (-120)
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O 44 (-107)
U 44 (-113)
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–
–
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-150
+130
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-3 (+100)
+3 (-120)
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O 44.5 (-110)
U 44.5 (-110)
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–
–
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-130
+110
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-2 (-110)
+2 (-110)
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O 52.5 (-110)
U 52.5 (-110)
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Nov 2, 2025 8:20PM EST
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-163
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-3 (-113)
+3 (-107)
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O 48 (-110)
U 48 (-110)
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Nov 3, 2025 8:15PM EST
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Cardinals
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–
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+130
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-2.5 (-115)
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O 53.5 (-105)
U 53.5 (-115)
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–
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+370
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O 42.5 (-110)
U 42.5 (-110)
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+290
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O 48.5 (-110)
U 48.5 (-110)
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NFL Past Picks
Remi—our in-house AI—prices every game and prop using multi-season priors, tempo/efficiency, injury/usage signals, and market movement.
We publish fair prices, recommended “buy-to” numbers, and confidence so you can bet prices, not teams.
This preview covers Jacksonville Jaguars vs. San Francisco 49ers on September 28, 2025 at Levi's Stadium.
Odds shown reflect widely available numbers and may update closer to kickoff.
Want more? Check live edges, player props, and line moves on our NFL odds pages, and compare prices before you place a bet.
| LEAN | %WIN | UNITS | RESULT | |
|---|---|---|---|---|
| TB@NO | TB -3.5 | 52.3% | 1 | WIN |
| GB@PIT | GB -2.5 | 52.3% | 1 | WIN |
| SF@HOU | SF +2.5 | 56.0% | 6 | LOSS |
| NYG@PHI | NYG +7.5 | 53.9% | 3 | LOSS |
| BUF@CAR | CAR +7.5 | 54.2% | 3 | LOSS |
| DAL@DEN | DAL +3.5 | 55.0% | 4 | LOSS |
| MIA@ATL | MIA +7 | 54.3% | 4 | WIN |
| CLE@NE | CLE +7 | 56.8% | 6 | LOSS |
| TB@NO | BAKER MAYFIELD OVER 15.5 RUSH YDS | 56.6% | 6 | LOSS |
| MIN@LAC | JUSTIN HERBERT PASS ATT UNDER 35.5 | 55.5% | 5 | WIN |
| TB@DET | TB +6.5 | 54.4% | 4 | LOSS |
| TB@DET | RACHAAD WHITE UNDER 14.5 RUSH ATT | 54.4% | 4 | WIN |
| NE@TEN | NE -6.5 | 55.2% | 5 | WIN |
| CAR@NYJ | CAR -110 | 57.4 | 4 | WIN |
| PHI@MIN | PHI -130 | 58.0% | 6 | WIN |
| GB@ARI | ARI +7 | 54.8% | 5 | WIN |
| NO@CHI | NO +4.5 | 57.4% | 7 | LOSS |
| WAS@DAL | JAYDEN DANIELS 1H RUSH YDS OVER 22.5 | 56.1% | 5 | WIN |
| GB@ARI | JORDAN LOVE 1Q PASS YDS OVER 54.5 | 56.6% | 6 | WIN |
| PIT@CIN | JONNU SMITH RECEPTIONS OVER 3.5 | 55.3% | 5 | LOSS |
| BUF@ATL | BUF -3.5 | 54.7% | 4 | LOSS |
| CHI@WAS | JAYDEN DANIELS OVER 1.5 PASS TDS | 56.6% | 6 | WIN |
| TEN@LV | UNDER 42 | 54.8% | 3 | WIN |
| DET@KC | DET +2.5 | 55.7% | 7 | LOSS |
| SEA@JAC | SEA -112 | 55.7% | 5 | WIN |
| LAC@MIA | LAC -3.5 | 54.0% | 3 | LOSS |
| ARI@IND | IND -8.5 | 55.6% | 5 | LOSS |
| TEN@LV | TEN +4.5 | 56.7% | 6 | LOSS |
| LAR@BAL | LAR -7 | 56.2% | 6 | WIN |
| SF@TB | SF +3.5 | 57.2% | 7 | LOSS |
| CLE@PIT | JAYLEN WARREN UNDER 46.5 RUSH YDS | 54.4% | 4 | LOSS |
| DEN@NYJ | BREECE HALL OVER 26.5 RECV YDS | 55.0% | 4 | LOSS |
| KC@JAC | UNDER 45.5 | 54.9% | 3 | LOSS |
| KC@JAC | PATRICK MAHOMES UNDER 23.5 PASS COMP | 56.6% | 6 | LOSS |
| HOU@BAL | HOU -125 | 58.5% | 7 | WIN |
| DET@CIN | DET -10 | 55.6% | 5 | WIN |
| DAL@NYJ | NYJ +1.5 | 53.7% | 3 | LOSS |
| TB@SEA | TB +3.5 | 54.9% | 4 | WIN |
| TEN@ARI | ARI -7 (BUY 0.5) | 54.9% | 4 | LOSS |
| DEN@PHI | DEN +4.5 | 57.5% | 7 | WIN |
| MIA@CAR | TETAIROA MCMILLAN OVER 58.5 RECV YDS | 54.5% | 4 | WIN |
| LV@IND | ASHTON JEANTY UNDER 67.5 RUSH YDS | 54.4% | 4 | WIN |
| SF@LAR | DEMARCUS ROBINSON OVER 29.5 RECV YDS | 55.7% | 5 | WIN |
| NYJ@MIA | NYJ +3 | 53.8 | 3 | LOSS |
| CIN@DEN | DEN -7.5 | 54.8 | 4 | WIN |
| NYJ@MIA | OVER 44 | 52.9% | 2 | WIN |
| CIN@DEN | UNDER 44.5 | 53.7% | 3 | WIN |
| NYJ@MIA | GARRETT WILSON UNDER 9 TARGETS | 53.7% | 3 | WIN |
| CIN@DEN | TEE HIGGINS OVER 6.5 RECV TARGETS | 55.5% | 5 | LOSS |
| WAS@ATL | ATL -2.5 | 54.3 | 4 | WIN |
| BAL@KC | BAL -2.5 | 56.3% | 6 | LOSS |