The November 9, 2025 clash between the Los Angeles Rams and the San Francisco 49ers at SoFi Stadium stands as one of the marquee matchups of Week 10, not only because of its divisional implications but because it renews one of the NFC’s fiercest rivalries between two franchises that know each other inside and out. The Rams enter the game looking like one of the NFC’s most improved teams, rejuvenated by a strong mix of veteran leadership and emerging young talent, while the 49ers, despite their pedigree and star power, are navigating a season defined by inconsistency, injuries, and the pressure to live up to Super Bowl expectations. Los Angeles, under Sean McVay, has found a rhythm that feels like a return to form—quarterback Matthew Stafford has been sharp, decisive, and in sync with his evolving group of weapons. The breakout of second-year wide receiver Puka Nacua has transformed the Rams’ offense into a dynamic, multi-level threat, as his chemistry with Stafford gives defenses fits across the middle of the field. The return of Cooper Kupp to full health adds another layer of complexity, as his precision route running and spatial awareness remain elite. On the ground, Kyren Williams has become a reliable workhorse, offering the balance that McVay’s system thrives on when both the run and pass are respected. The Rams’ offensive line, a weakness in recent years, has solidified, providing Stafford with time to operate while opening consistent rushing lanes. Defensively, the Rams continue to evolve post-Aaron Donald, leaning on youth and speed to create pressure while maintaining a disciplined structure. Rookie edge rusher Jared Verse has been impressive, while Ernest Jones anchors a defense that has played with surprising cohesion. Facing San Francisco, the Rams know they must neutralize Christian McCaffrey, whose versatility as both a runner and receiver remains the cornerstone of Kyle Shanahan’s offense.

The 49ers’ offensive rhythm lives and dies by McCaffrey’s touches and the timing of quarterback Brock Purdy, whose poise and efficiency have kept the team afloat despite a rash of injuries. Purdy has demonstrated the same quick decision-making and pocket control that made him a breakout star, but he has also shown vulnerability when pressured—something the Rams’ front will aim to exploit. Wide receivers Deebo Samuel and Brandon Aiyuk provide explosive options on the outside, and tight end George Kittle remains Purdy’s safety valve in critical situations. Defensively, the 49ers’ identity is built around dominance at the line of scrimmage, led by Nick Bosa, Javon Hargrave, and Fred Warner. However, their secondary has been tested in recent weeks, giving up chunk plays that have kept opponents in games longer than expected. Against the Rams, the 49ers’ front must generate pressure without overcommitting, as Stafford has historically excelled against heavy blitzes by exploiting single coverage downfield. The chess match between McVay and Shanahan will once again define this contest: McVay’s offensive innovation versus Shanahan’s defensive adjustments and ball-control tactics. Special teams could also play a decisive role, as both sides have relied heavily on field position and long drives to close out wins. The rivalry’s recent history favors San Francisco, which has dominated in the regular season, but the Rams’ current form and home-field advantage make this a more even contest than the record books suggest. Ultimately, the outcome will hinge on who dictates tempo—if the Rams’ offense can sustain drives and protect Stafford, they can outscore the 49ers in a high-efficiency, balanced performance; if San Francisco’s defense imposes its physical will and forces turnovers, the 49ers’ playoff-caliber experience could prevail. In a matchup that rarely disappoints, expect a physical, high-stakes battle where every snap carries weight, and the victor not only gains ground in the NFC West but sends a message about their place among the conference’s elite.