The San Francisco 49ers enter their pivotal Week 10 divisional showdown against the Los Angeles Rams with momentum, having won five of their last six games despite missing their franchise quarterback for most of the season. At 6-3 and riding the arm of backup Mac Jones, the Niners host the surging 6-2 Rams at Levi's Stadium in what projects as the highest-scoring game of Week 10, with oddsmakers setting the total at 49.5 points.
While the 49ers are 3.5-point underdogs at home, this rivalry has belonged to Kyle Shanahan recently, as the San Francisco head coach owns a 10-6 all-time record against his former assistant Sean McVay. The teams last met in Week 5, when a shorthanded 49ers squad stunned Los Angeles 26-23 in overtime at SoFi Stadium. With both teams fighting for NFC West supremacy and playoff positioning, this rematch promises fireworks.
Here are three bold predictions for Sunday's blockbuster clash.
Christian McCaffrey Will Eclipse 150 Total Yards and Score Twice
Christian McCaffrey has been the 49ers' offensive lifeline throughout their injury-plagued season. The star running back is averaging 66.2 rushing yards per game while compiling 596 yards on the ground with four touchdowns through nine games. In the first matchup against the Rams, McCaffrey totaled 139 yards from scrimmage and was instrumental in San Francisco's overtime victory.
The Rams defense has struggled against dynamic running backs this season, allowing 108.9 rushing yards per game and ranking 18th in the league. McCaffrey's versatility as both a runner and receiver makes him impossible to game-plan against, especially in Shanahan's creative scheme. With Mac Jones likely starting again at quarterback and Brandon Aiyuk still sidelined with a knee injury, expect Shanahan to lean heavily on his All-Pro back.
McCaffrey will exploit Los Angeles' suspect run defense and find the end zone twice while surpassing 150 total yards, continuing his dominance in this rivalry.
Matthew Stafford Will Throw for 350+ Yards but Suffer Two Costly Turnovers
Matthew Stafford enters Week 10 playing at an MVP-caliber level, having thrown 21 touchdowns against just two interceptions through eight games with a spectacular 113.2 passer rating. The 37-year-old quarterback has been surgical, averaging 268.4 passing yards per game and posting a remarkable 67.2 completion percentage. In his last outing against New Orleans, Stafford threw four touchdowns and posted a gaudy 140.8 passer rating.
Matthew Stafford no-looking a deep dig pic.twitter.com/VcdXgDeVid
— Nate Tice (@Nate_Tice) November 2, 2025
However, the 49ers defense—despite their injuries—has historically given Stafford problems. San Francisco's defense allows just 223.7 passing yards per game and ranks among the league's best at generating pressure. The Niners held Stafford to 389 yards in the first meeting but forced crucial mistakes, including a goal-line fumble by Kyren Williams that helped preserve the overtime victory.
While Stafford will rack up yardage against a depleted secondary working overtime with Puka Nacua and potentially Davante Adams, the 49ers' opportunistic defense will force two turnovers at critical moments. Expect San Francisco's defensive front to dial up pressure and create chaos, leading to game-altering mistakes from an otherwise brilliant quarterback.
The 49ers Will Win in a Shootout, Covering the Spread as Home Underdogs
This bold prediction defies conventional wisdom, but the 49ers have made a habit of proving doubters wrong this season. Mac Jones has gone 5-2 as a starter, completing 67.2% of his passes for 1,832 yards with 10 touchdowns and five interceptions. More importantly, Jones thrives in Kyle Shanahan's system and already beat this Rams team once in Week 5, throwing for 342 yards and two touchdowns in the overtime thriller.
The Rams are 6-2 and winners of three straight, but their only road wins came against Tennessee, Baltimore without Lamar Jackson, and Jacksonville—hardly impressive résumé builders. Los Angeles also has a Sean McVay problem: the head coach is now 0-6 against Shanahan since 2019 and trails 10-6 all-time in this rivalry. The psychological edge clearly favors San Francisco.
With the over/under set at 49.5 points, expect an offensive explosion from both sides. But the 49ers will get crucial contributions from Kendrick Bourne, who torched the Rams for 142 yards in the first meeting, and George Kittle, who has been limited but effective with 100 yards and two touchdowns in limited action this season. San Francisco's defense will bend but not break, creating timely turnovers that swing momentum.
The 49ers will win 31-27, covering the 3.5-point spread and extending their dominance over their division rivals while keeping pace in the NFC West race.
Sunday's clash represents more than just a divisional game—it's a statement opportunity for both franchises. The Rams seek revenge and validation of their impressive start, while the 49ers aim to prove they remain the NFC West's alpha despite their injury adversity. With playoff implications on the line and one of the NFL's fiercest coaching rivalries renewed, this blockbuster matchup has all the ingredients for an instantor an instant classic.
