Predicting the winner of the 49ers' Week 10 game against the Rams

History predicts a close one

Oct 2, 2025; Inglewood, California, USA; Los Angeles Rams quarterback Matthew Stafford (9) drops back to pass against the San Francisco 49ers during the first half at SoFi Stadium. Mandatory Credit: Kirby Lee-Imagn Images | Kirby Lee-Imagn Images

Six of the last nine games between the 49ers and Rams have been decided by three points or fewer. The key to victory depends on who you ask. 49ers defensive coordinator Robert Saleh says the teams know each other so well it comes down to execution that day. George Kittle says it’s about physicality and who wants it more.

On paper, the Rams should win this game; but on paper, the Rams should have won the first matchup in Week 5.

49ers on Offense

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The first key is winning with the short passing game. In the first matchup, Mac Jones was 22-27 from 1 to 7 yards. He completed 7 of 10 middle, 2-3 right, and thrived throwing left at 13-14. The Rams rank 7th in the league in pass defense middle, but the Niner middle passing game is ranked higher. San Francisco won that matchup the first time out and will need to do so again.

The second key is Jones getting the ball out before the LA pass rush arrives. Jones was only sacked once in week five, going 33-49 for 340 yards and 2 TDs. Kittle didn’t play in that game, he’ll need to be a focal point this time.

The third key is success on first down. The Ram defense is one of the league’s best on first, setting up 2nd and long, 3rd and long, enabling their pass rush to go hunting. What makes the Ram front unique is its versatility, solid both in pressuring the quarterback and stopping the run. The Niners need to get consistent gains on first to avoid obvious passing downs.

Christian McCaffrey had 57 yards on 22 carries with a long of just eight in Week Five. The Niner run game will need to be much more efficient and consistent. Kittle’s return, the improved play of Trent Williams, and the reunion of the starting offensive line will help the Niners have more success on the ground this time around.

The Rams defense is 2nd in the league in the red zone, only giving up a touchdown on 39.1% of red zone drives. The Niners' red zone offense has improved in recent weeks, and Kittle will once again be key.

Rams on Offense

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Without Fred Warner, Nick Bosa, Mykel Williams, and potentially Alfred Collins (he’s missed the last two practices), Saleh has little to work with in this matchup. With the defense this short-handed, beating the Rams may depend on bend but don’t break success, field goals not touchdowns.

The first defensive key is finding ways to pressure Matthew Stafford. The Niners get Bryce Huff back and hope they’ll get production from new additions Keion White on the inside pass rush (if he plays, listed as questionable) and Clelin Ferrell setting the edge.

Saleh will need to employ simulated pressure to keep the offense guessing where the pressure will come from, and blitzes need to send speed. Blitzing Ji’Ayir Brown hasn’t worked to date; he’s too slow to close. Upton Stout and Chase Lucas need to time up blitzes to pursue Stafford unblocked in time to disrupt the play.

If the Niners fail to generate stops on 3rd, it’ll be a replay of the Houston game, giving up too many long drives and scores. Saleh will need to take more risks. Playing soft zone coverage to prevent explosive plays won’t work against LA given Stafford’s accuracy and the skill of the receivers.

Stafford has been playing MVP football the past five weeks, completing two-thirds of his passes for over 280 yards and three touchdowns per game with no picks. Davante Adams has five touchdowns in the past two games. Puka Nakua has been dealing with a chest injury but was a full participant in practice on Thursday.

The second defensive key is stopping the run. Kyren Williams had 14 carries for 65 yards in Week Five. He’s coming off his first 100-yard game of the season, 114 on 25 carries against New Orleans. If the Rams establish run-pass balance, they’ll win. Saleh needs to bring the secondary up to fill against the run.

Prediction (4-5)

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The Niners are capable of scoring consistently, provided Kittle has a big game. It’s the defense that will struggle. Stafford is playing exceptionally well, and the Niners are last in the league in pressure rate. I expect the Rams to be fired up for payback in this one. The Niners hope they can hang around by matching scores, but if they give up several long drives, the defense won’t have their legs in the 4th to close the game.

Rams 27 Niners 20