49ers vs. Rams Prediction, Odds & Picks for Sept. 10: Stafford Leads Rams to Win
Week 1 of the NFL season rolls on with a game down under between NFC West rivals as the San Francisco 49ers take on the Los Angeles Rams in Melbourne Thursday night, and we have you covered with our 49ers vs. Rams prediction. San Francisco finished the 2025 season 12-5 and finished tied for second in the NFC West. Their season ended with a 41-6 demolition by Seattle in the NFC Divisional Round.
Los Angeles finished 2025 12-5 and finished tied for second in the NFC West. Their season finished with a 31-27 road defeat to the Seahawks in the NFC Championship Game. In the all-time regular-season series between the teams, the 49ers own a 78-71-3 advantage. However, the Rams won four of the last five meetings, including a 42-26 road win in the most recent matchup on November 9, 2025. Read on to get our 49ers vs. Rams prediction.
San Francisco 49ers Trying to Set Tone Early
49ers 2025 Season in Review
San Francisco managed to finish 12-5 despite injury issues taking a toll on the skill players on both sides of the ball. Brock Purdy missed eight games but was 7-2 in his starts. Meanwhile, Mac Jones was solid enough in relief, posting a 5-3 mark in his eight starts. Jauan Jennings missed a pair of games, George Kittle missed six, and Brandon Aiyuk never saw the field at all.
Defensively, Nick Bosa played just three games while Fred Warner was active for only six. Despite it all, the 49ers beat the Eagles in the Wild Card round before taking a pasting at the hands of the Seahawks.
Changes in the Mix for 2026 for San Francisco
In 2025, the 49ers ranked 5th in the league in passing, averaging 244.5 yards per game through the air. San Francisco was 24th in the league in rushing offense as they piled up 106.9 yards per game on the ground last season. The 49ers ranked 10th in the league in scoring offense, averaging 25.7 points per game. San Francisco was 13th in the league in scoring defense by allowing an average of 21.8 points per contest.
Brock Purdy finished 197-for-284 passing for 2,167 yards with 20 touchdowns and 10 interceptions while getting sacked 11 times. He added 147 yards and three scores on the ground. Mac Jones (201 of 289, 2,151 yards, 13 TD, six INT, 63 rush yards) has stepped up with Purdy missing time. Christian McCaffrey led the ground game with 311 carries for 1,202 yards and 10 scores. With Isaac Guerendo hurt, rookie third-round pick Kaelon Black is the backup.
Meanwhile, the starting receivers have been overhauled since last year. Mike Evans (30 catches, 368 yards, three TDs with Tampa Bay), Deebo Samuel (72 grabs, 727 yards, five TDs with Washington), and rookie De’Zhaun Stribling. Kittle (57 catches, 628 yards, seven TDs) is the starting tight end. Eddy Piniero hit 34 of 38 extra point attempts and 28 of 29 field goal attempts with a long of 59 last year.
Check out San Francisco 49ers odds for the 2026-27 season.
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Rams 2025 Season in Review
Los Angeles went 12-5 last season and came within a game of the Super Bowl. Their hopes were dashed with an NFC Championship Game loss to the Seahawks on the road at Lumen Field. To be fair, the Rams may have been fortunate to get to that point. After all, they squeaked past Carolina 34-31 in the wild card round.
Meanwhile, they needed overtime to get past the Bears in the divisional round. They simply ran out of luck when it came to crunch time against the Seahawks. Matthew Stafford earned NFL MVP honors but seeks to add another Super Bowl ring to his resume.
2026 Rams Super Bowl Favorites
The Rams finished last season 1st in the league in passing offense, averaging 268.1 yards per game through the air, and 7th in rushing offense, averaging 126.6 yards per game. Los Angeles ranked 1st in the league in scoring offense, averaging 30.5 points per game, while ranking 10th in scoring defense, allowing 20.4 points per game.
Matthew Stafford hit 388 of 597 passes for 4,707 yards with 46 touchdowns against eight interceptions. He was sacked 23 times. Kyren Williams led the team on the ground with 259 carries for 1,252 yards and 10 scores last year. Blake Corum (145 carries, 746 yards, six TDs) is the second back in the system. Puka Nacua (129 catches, 1715 yards, 10 TDs) was the team’s leading receiver.
Davante Adams (60 receptions, 789 yards, 14 TDs) and Williams (36 grabs, 281 yards, three TDs) provide solid options. The tight end group of Colby Parkinson (43 grabs, 408 yards, eight TDs), Terrance Ferguson, and Tyler Higbee (25 catches, 281 yards, three TDs) is all valuable options in the passing game. Harrison Mevis hit 39 of 39 extra point attempts and 12 of 13 field goal attempts with a long of 52 as a rookie.
We have full Los Angeles Rams odds for the new campaign.
49ers vs. Rams Prediction
Rams -3.5 (Fanatics, -110)
This is a 49ers team that is trying to patch things up on the fly. Two of their top four receivers are on injured reserve already. Christian Kirk should return; however, Ricky Pearsall is done for the year. None of the three starting receivers were on the team last year. In addition, San Francisco has injury concerns on defense. The Rams won’t have Aaron Donald in this contest, but they do have Myles Garrett to make things difficult. Los Angeles has all the firepower they need from last year’s offensive squad. You have to think that the Rams live up to the billing here and open the year 1-0.
Fanatics Sportsbook lists the Rams as 3.5-point favorites, and we're taking that for the TNF matchup.
Under 48.5 (BetMGM, -110)
If Wednesday night’s game was any indication, points may be hard to come by. Both meetings between these teams were high-scoring affairs a year ago, but they were played stateside. It’s hard to know how much the massive time difference between the West Coast and Australia will impact the teams. Both defenses were above average last season in limiting points allowed. With that in mind, and factoring in the travel involved for this contest, it may not take more than 24 points to win this contest. Therefore, take the Under 48.5 points at BetMGM Sportsbook in this one.
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