The Los Angeles Rams and San Francisco 49ers will play one another in Week 10 of the NFL season on Sunday. The Rams come in at 6-2 after a convincing 34-10 win over the Saints. The 49ers sit at 6-3 after a win over the New York Giants. The winner of this game will be ahead of the loser in the NFC West standings. Below you will find my Rams vs 49ers prediction for this huge game in the NFC playoff race.
Our Rams vs 49ers Pick
- Pick: 49ers +4.5
- Confidence: ★★★☆☆
Game Snapshot
- Matchup: Los Angeles Rams vs San Francisco 49ers
- Date & Time: Sunday, November 9, 2025, 4:25 p.m. ET
- Venue: Levi’s Stadium, Santa Clara, CA
- Broadcast: FOX
Key Storylines
Los Angeles has won three games in a row coming into this week. They have shut down the Ravens, Jaguars, and Saints over those three games. This will be a bigger challenge for Los Angeles as they look to prove that their defense can also stand up to teams in the playoff hunt. The Rams are 3-1 on the road so far this season and will try to pass their biggest road test of the season to date here.
The 49ers defeated the New York Giants on the road last week to get to 6-3. They’ve been hit hard by injuries on defense. Losing Nick Bosa early in the year was tough and the loss of linebacker Fred Warner might be even more damaging. San Francisco’s defense has given up big plays through the air recently. The Niners will have to get pressure on Matthew Stafford to prevent him from having time to complete throws down the field.
Quarterback Play
Matthew Stafford looks healthy and confident again. His four-touchdown day against New Orleans last week showed the kind of precision and rhythm that made him one of the league’s top quarterbacks throughout his career. The Rams can beat anyone if they protect Stafford and give him time to stretch the field vertically.
Brock Purdy is dealing with a toe and shoulder issue. He’s expected to start but the Niners could turn to Mac Jones if Purdy isn’t at 100%. Both quarterbacks for the 49ers are serviceable and they have the help of the dynamic Christian McCaffrey out of the backfield to make things easier on them.
Betting Trends & H2H
- Rams are 6-2 against the spread this year.
- The 49ers are 5-4 against the spread going into this matchup.
- The over has hit in five of San Francisco’s first nine games (5-3-1).
- The under has cashed in five of the Rams’ eight games this season.
- The 49ers won the first meeting between these teams this season, 26-23 in overtime at SoFi Stadium.
Rams vs 49ers Model Projection
Projected Score: Rams 27 – 49ers 24
Win Probability: Rams 62% | 49ers 38%
Final Thoughts
I would be shocked if we didn’t see another very close game between these two NFC West teams. The Niners are dealing with some major injuries on defense. But I am still going to take the points with San Francisco in this game. This feels like a field goal game no matter which team gets the win in Santa Clara.
