Cardinals vs. Giants
Prediction, Odds & Props
Sep 22 | MLB AI Picks
Updated: 2025-09-20T03:31:50.923562ZBy Remi at Leans.AI — AI picks for ATS, ML, OU & props
The Cardinals travel to San Francisco trying to turn around a rough stretch, facing a Giants squad that’s played solid baseball at home and is motivated to defend Oracle Park. With both teams still in flux—St. Louis battling inconsistency and the Giants trying to build momentum—this feels like a game where pressure, bullpen work, and offensive discipline will decide more than raw talent.
Get key insights, betting trends, and AI-powered predictions to help incorporate into your betting strategies.
GAME INFO
Date: Sep 22, 2025
Start Time: 9:45 PM EST
Venue: Oracle Park
Giants Record: (77-79)
Cardinals Record: (76-80)
OPENING ODDS
STL Moneyline: +123
SF Moneyline: -148
STL Spread: +1.5
SF Spread: -1.5
Over/Under: 8
STL
Betting Trends
- St. Louis has shown moderate success against the spread in their recent games; their ATS record in the last 10 or so outings is slightly above .500, indicating that while they may lose tougher matchups, they often perform better than oddsmakers expect.
SF
Betting Trends
- The Giants at home are a mixed bag when it comes to covering the spread. Their record at Oracle Park this season shows some wins and some losses, and their ATS mark at home is not overwhelmingly strong, suggesting bettors should be cautious about assuming home-field dominance will automatically translate into covering.
MATCHUP TRENDS
- This matchup offers a few betting angles worth noting. First, when the Giants are favored modestly at home, they often win the game, but sometimes fail to cover large spreads. Second, St. Louis has performed decently as underdog in similar road games, which could offer value on the run line if the spread is favorable. Third, since both teams have had bullpen troubles at times, especially in high-leverage situations, this could be one of those tight games where late-inning pitching determines the outcome—and that often leads to closer-than-expected finishes, possibly favoring totals on high-scoring but shaky finishes.
STL vs. SF
Best Prop Bet
- Remi's searched hard and found the best prop for this matchup: P. Pages over 0.5 Hits+Runs+RBI.
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St. Louis vs San Francisco Prediction & Odds:
Free MLB Betting Insights for 9/22/25
Their starting pitcher will need to set the tone, throwing strikes early and keeping the Giants’ lineup off balance, because falling behind in San Francisco is usually a recipe for defeat. Defensively, the Cardinals must be sharp, as errors have been a problem in their losses and the Giants are adept at turning extra outs into crooked innings. From a betting perspective, the Giants are expected to be slight favorites at home, but their mixed ATS record at Oracle Park suggests that margin of victory is far from certain, particularly against a Cardinals team that tends to hang around. The keys to this matchup are clear: San Francisco must capitalize on scoring chances and rely on their bullpen to protect a lead, while St. Louis must lean on steady starting pitching and opportunistic offense to neutralize the home-field edge. In the end, this looks like a game that could tilt either way depending on execution in the middle innings, and while the Giants hold the advantage on paper, the Cardinals’ ability to grind out at-bats and stay disciplined could make for a tense, closely contested finish.
That was for the fans... That's a Winner! pic.twitter.com/Ocwk4s1MyC
— St. Louis Cardinals (@Cardinals) September 21, 2025
St. Louis Cardinals MLB Preview
The St. Louis Cardinals arrive at Oracle Park on September 22, 2025, looking to play spoiler in a season that has seen them battle inconsistency but also showcase flashes of resilience, especially in tight games on the road where they’ve managed to hang around longer than expected. Their success in this matchup will depend heavily on the performance of their starting pitcher, who must attack the strike zone, keep Giants hitters off balance, and avoid falling behind early, as playing catch-up in San Francisco is a steep uphill climb. Offensively, the Cardinals don’t rely on pure power but instead thrive when they can extend innings, string together base hits, and execute situational hitting, an approach that can frustrate a Giants staff that has occasionally struggled with command. Key bats in the middle of the lineup will need to step up and drive in runs when chances arise, because leaving men stranded has been a recurring issue and one that often leads to narrow defeats.
Defensively, St. Louis must remain sharp and avoid errors, as lapses in the field have cost them dearly this year and the Giants are particularly good at capitalizing on mistakes to spark big innings. The bullpen, while uneven, has the potential to hold games close if handed a manageable situation, though late-inning collapses have been an issue when relievers are overworked. From a betting perspective, the Cardinals are clear underdogs, but their knack for keeping games close makes them an intriguing run-line option, especially if the Giants’ offense sputters or their bullpen falters under pressure. To pull off an upset, St. Louis will need a strong outing from their starter, timely hitting from the middle of the order, and clean defense to keep San Francisco from gaining momentum. If they can execute those fundamentals, they may not only stay within the spread but could also steal a road victory that would serve as a morale boost late in the season.
Credit: USA TODAY/IMAGN
San Francisco Giants MLB Preview
The San Francisco Giants return to Oracle Park on September 22, 2025, with the advantage of home field and the urgency of finishing their season strong, leaning on their ability to generate offense in spurts and ride the energy of their crowd to put pressure on the visiting Cardinals. Their lineup has been streaky but dangerous, with several bats capable of changing a game in one swing, and the key for San Francisco will be capitalizing on early scoring opportunities to build momentum and force St. Louis into a reactive game plan. The Giants’ starter will be tasked with delivering a steady outing by limiting walks, working efficiently through the order, and setting up the bullpen with a lead to protect, because while their relievers have shown flashes of dominance, inconsistency in high-leverage innings has left them vulnerable to late collapses. Offensively, San Francisco needs to avoid stranding runners, an issue that has cost them games, and instead focus on situational hitting and aggressiveness on the basepaths to manufacture runs in tight spots.
Defensively, playing clean baseball will be critical, as the Cardinals thrive on opponents’ mistakes to extend innings, and any lapse could flip the game quickly. From a betting standpoint, the Giants are likely to be favored at home, but their mixed record against the spread at Oracle Park shows that wins have not always been comfortable or by wide margins, making run-line bets riskier than moneyline plays. Their formula for success lies in striking first, maintaining discipline at the plate, and trusting the bullpen to hold together under pressure, all while using the familiarity of their home field to dictate tempo. If they execute cleanly in all phases, San Francisco should have enough balance to secure the win, but if their offense goes quiet or the bullpen falters, the door will remain open for St. Louis to make this game closer than expected.
#SFGiants win 👏#SFGiants | @budweiserusa pic.twitter.com/GTrQ7SpUrm
— SFGiants (@SFGiants) September 21, 2025
St. Louis vs. San Francisco Prop Picks (AI)
St. Louis vs. San Francisco Prediction (AI)
Remi, our AI sports wizard, has been pouring over exorbitant amounts of data from every angle between the Cardinals and Giants and using recursive machine learning and impressive AI to analyze the data to a single cover probability.
Oddly enough, we’ve seen the AI has been most focused on the linear correlation of weight human bettors often put on coaching factors between a Cardinals team going up against a possibly rested Giants team. It appears the true game analytics might reflect a moderate lean against one Vegas line specifically.
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Below is our current AI St. Louis vs San Francisco picks, computer picks Cardinals vs Giants, best bets, model edges, confidence ratings.
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DATE | GAME | LEAN | %WIN | UNITS | LEVEL |
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| MLB | 10/1 | SD@CHC | UNLOCK THIS PICK | 4 |
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| MLB | 10/1 | SD@CHC | UNLOCK THIS PICK | 4 |
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| MLB | 10/1 | CIN@LAD | UNLOCK THIS PICK | 3 |
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| MLB | 10/1 | CIN@LAD | UNLOCK THIS PICK | 2 |
INTEL
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| MLB | 10/1 | DET@CLE | UNLOCK THIS PICK | 2 |
INTEL
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| MLB | 10/1 | DET@CLE | UNLOCK THIS PICK | 1 |
INTEL
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| MLB | 10/1 | BOS@NYY | UNLOCK THIS PICK | 1 |
INTEL
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| MLB | 10/1 | CIN@LAD | GET FREE PICK NOW | 1 | – | |
| MLB | 10/1 | BOS@NYY | UNLOCK THIS PICK | 0 |
INTEL
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| MLB | 10/1 | BOS@NYY | GET FREE PICK NOW | 0 | – | |
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 MLB schedule.
Cardinals Betting Trends
St. Louis has shown moderate success against the spread in their recent games; their ATS record in the last 10 or so outings is slightly above .500, indicating that while they may lose tougher matchups, they often perform better than oddsmakers expect.
Giants Betting Trends
The Giants at home are a mixed bag when it comes to covering the spread. Their record at Oracle Park this season shows some wins and some losses, and their ATS mark at home is not overwhelmingly strong, suggesting bettors should be cautious about assuming home-field dominance will automatically translate into covering.
Cardinals vs. Giants Matchup Trends
This matchup offers a few betting angles worth noting. First, when the Giants are favored modestly at home, they often win the game, but sometimes fail to cover large spreads. Second, St. Louis has performed decently as underdog in similar road games, which could offer value on the run line if the spread is favorable. Third, since both teams have had bullpen troubles at times, especially in high-leverage situations, this could be one of those tight games where late-inning pitching determines the outcome—and that often leads to closer-than-expected finishes, possibly favoring totals on high-scoring but shaky finishes.
St. Louis vs. San Francisco Game Info
What time does St. Louis vs San Francisco start on September 22, 2025?
St. Louis vs San Francisco starts on September 22, 2025 at 9:45 PM EST.
Where is St. Louis vs San Francisco being played?
Venue: Oracle Park.
What are the opening odds for St. Louis vs San Francisco?
Spread: San Francisco -1.5
Moneyline: St. Louis +123, San Francisco -148
Over/Under: 8
What are the records for St. Louis vs San Francisco?
St. Louis: (76-80) | San Francisco: (77-79)
What is the AI best bet for St. Louis vs San Francisco?
Remi's searched hard and found the best prop for this matchup: P. Pages over 0.5 Hits+Runs+RBI.. Prices move—always shop for the best number.
What are St. Louis vs San Francisco trending bets?
This matchup offers a few betting angles worth noting. First, when the Giants are favored modestly at home, they often win the game, but sometimes fail to cover large spreads. Second, St. Louis has performed decently as underdog in similar road games, which could offer value on the run line if the spread is favorable. Third, since both teams have had bullpen troubles at times, especially in high-leverage situations, this could be one of those tight games where late-inning pitching determines the outcome—and that often leads to closer-than-expected finishes, possibly favoring totals on high-scoring but shaky finishes.
What are St. Louis trending bets?
STL trend: St. Louis has shown moderate success against the spread in their recent games; their ATS record in the last 10 or so outings is slightly above .500, indicating that while they may lose tougher matchups, they often perform better than oddsmakers expect.
What are San Francisco trending bets?
SF trend: The Giants at home are a mixed bag when it comes to covering the spread. Their record at Oracle Park this season shows some wins and some losses, and their ATS mark at home is not overwhelmingly strong, suggesting bettors should be cautious about assuming home-field dominance will automatically translate into covering.
Where can I find AI Picks for St. Louis vs San Francisco?
See our latest MLB picks and odds pages for 2025 to compare prices before you bet.
St. Louis vs. San Francisco Odds
AI algorithm Remi is pouring through tons of data on each line. In fact, anytime the St. Louis vs San Francisco trends are analyzed, there’s always several intriguing observations to key in on. Not to mention games played at extreme hostile environments seemingly never follow normal, predictable betting trends.
St. Louis vs San Francisco Opening Odds
STL Moneyline:
+123 SF Moneyline: -148
STL Spread: +1.5
SF Spread: -1.5
Over/Under: 8
St. Louis vs San Francisco Live Odds
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Cleveland Guardians
10/2/25 3:08PM
Tigers
Guardians
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–
–
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+100
-120
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-1.5 (+175)
+1.5 (-215)
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O 7 (-105)
U 7 (-115)
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+100
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-1.5 (+172)
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–
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+136
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+1.5 (-160)
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O 7.5 (-120)
U 7.5 (-102)
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Oct 4, 2025 2:30PM EDT
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+110
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pk
pk
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Oct 4, 2025 5:09PM EDT
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10/4/25 5:09PM
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Phillies
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–
–
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+108
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pk
pk
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O 7 (-135)
U 7 (+115)
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MLB 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 St. Louis Cardinals vs. San Francisco Giants on September 22, 2025 at Oracle Park.
Odds shown reflect widely available numbers and may update closer to kickoff.
Want more? Check live edges, player props, and line moves on our MLB odds pages, and compare prices before you place a bet.
| MLB |
LEAN | %WIN | UNITS | RESULT |
|---|---|---|---|---|
| ARI@SD | SD -131 | 57.3% | 4 | WIN |
| DET@BOS | BOS -115 | 56.4% | 5 | WIN |
| NYM@CHC | NYM -110 | 54.1% | 3 | WIN |
| HOU@ATH | ATH +118 | 50.8% | 4 | WIN |
| NYM@CHC | OVER 7 | 54.5% | 3 | WIN |
| STL@SF | OVER 7.5 | 55.9% | 5 | LOSS |
| KC@LAA | TYLER TOLBERT UNDER 1.5 BASES | 54.4% | 4 | WIN |
| MIL@SD | UNDER 9 | 54.7% | 4 | WIN |
| MIA@PHI | KYLE SCHWARBER OVER 1.5 HITS+RUNS+RBIS | 53.3% | 3 | WIN |
| WAS@NYM | OVER 8.5 | 56.1% | 6 | LOSS |
| LAA@COL | COL +108 | 50.5% | 3 | WIN |
| TOR@KC | UNDER 9 | 54.7% | 4 | LOSS |
| SEA@KC | KC +1.5 | 62.3% | 5 | LOSS |
| NYY@MIN | OVER 9 | 55.1% | 4 | WIN |
| MIA@COL | OVER 10.5 | 55.0% | 4 | WIN |
| MIA@COL | AGUSTIN RAMIREZ OVER 1.5 HITS+RUNS+RBIS | 54.3% | 4 | WIN |
| SEA@KC | BOBBY WITT UNDER 0.5 SINGLES | 54.4% | 4 | LOSS |
| PHI@LAD | LAD -113 | 54.7% | 4 | LOSS |
| NYY@BOS | OVER 7.5 | 54.3% | 3 | WIN |
| KC@PHI | PHI -130 | 58.3% | 4 | WIN |
| LAD@SF | OVER 7.5 | 54.7% | 4 | LOSS |
| NYM@PHI | PHI -122 | 55.6% | 4 | WIN |
| KC@CLE | KC -104 | 52.0% | 3 | WIN |
| CIN@SD | JAKE CRONEWORTH OVER 0.5 HITS | 53.1% | 3 | WIN |
| WAS@MIA | MIA -123 | 55.2% | 4 | LOSS |
| LAA@KC | UNDER 9.5 | 54.9% | 3 | WIN |
| TEX@ARI | UNDER 9 | 54.2% | 4 | WIN |
| SF@COL | UNDER 11.5 | 56.4% | 6 | LOSS |
| SF@COL | RAFAEL DEVERS OVER 1.5 BASES | 56.1% | 6 | WIN |
| MIA@WAS | WAS -110 | 54.4% | 4 | WIN |
| NYM@DET | OVER 8.5 | 54.5% | 4 | WIN |
| TEX@ARI | UNDER 9.5 | 56.4% | 6 | WIN |
| TEX@ARI | ALEJANDRO OSUNA UNDER 1.5 BASES | 54.1% | 4 | LOSS |
| ATL@CHC | CHC -116 | 55.1% | 3 | WIN |
| PHI@MIL | OVER 8.5 | 55.0% | 3 | WIN |
| ARI@LAD | SHOHEI OHTANI OVER 2.5 BASES | 54.2% | 4 | WIN |
| SEA@CLE | CLE +1.5 | 57.2% | 3 | WIN |
| CHC@SF | CHC -105 | 54.1% | 4 | LOSS |
| NYY@CHW | RYAN MCMAHON OVER 0.5 BASES | 54.1% | 4 | WIN |
| PHI@NYM | OVER 8.5 | 55.6% | 4 | LOSS |
| LAA@TEX | LOGAN OHOPPE OVER 1.5 HITS+RUNS+RBIS | 54.1% | 4 | LOSS |
| KC@CHW | KC -109 | 54.2% | 4 | WIN |
| SD@SEA | DYLAN CEASE OVER 16.5 OUTS | 53.9% | 3 | LOSS |
| SD@SEA | UNDER 8.5 | 54.4% | 4 | LOSS |
| MIN@TOR | JOE RYAN UNDER 2.5 EARNED RUNS | 54.1% | 4 | LOSS |
| SF@MIL | MIL +100 | 54.0% | 6 | LOSS |
| TOR@MIA | MIA +1.5 | 62.0% | 6 | WIN |
| CHC@LAA | OVER 9.5 | 54.9% | 4 | LOSS |
| BOS@NYY | CARLOS RODON UNDER 4.5 HITS ALLOWED | 54.2% | 4 | WIN |
| KC@DET | DET -115 | 56.1% | 5 | WIN |
| CHC@LAA | LAA +1.5 | 57.6% | 5 | LOSS |