The San Francisco 49ers vs. Los Angeles Rams game is set to kick off at 8:35 p.m. ET on Thursday, September 10, at Melbourne Cricket Ground in Melbourne, Australia. The Rams enter as a 3.5-point favorite on the spread, via PrizePicks.
The Rams were within one victory of reaching the Super Bowl last season, falling to the Seahawks in the NFC Championship. Los Angeles is currently the favorite to win the Super Bowl (5x) this season, according to PrizePicks.
The 49ers were also eliminated by the Seahawks in the playoffs following a 12-5 campaign. San Francisco won six straight games before a home defeat in the season finale to Seattle, preventing the Niners from capturing the NFC West crown.
Below, we'll break down our 49ers vs. Rams prediction on the spread for Thursday's NFL game.
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49ers vs. Rams Prediction, Spread, Over/Under for Week 1 – Thursday, September 10
It’s tough to begin the season in Australia, much less in a division showdown. These rivals split a pair of meetings last season, with the road team winning each time.
San Francisco outlasted Los Angeles, 26-23, in overtime at SoFi Stadium in Week 5 as 7.5-point underdogs. QB Mac Jones led the 49ers with 342 yards and a pair of passing TDs, although he was outdone by Rams QB Matthew Stafford, who posted 389 yards and 3 TDs.
The Rams picked up revenge in the second matchup at Levi’s Stadium five weeks later, 42-26, to easily cover as 5.5-point favorites. Stafford threw 4 TDs to four different receivers as the Rams jumped out to a 21-0 lead.
The 49ers covered only three of eight times in the underdog role, while the Rams put together a solid 11-6 against the spread mark as a favorite.
San Francisco has RB Christian McCaffrey, TE George Kittle, and EDGE Nick Bosa all active. However, DT Alfred Collins suffered a season-ending knee injury this week.
For L.A., DT Aaron Donald returns to the Rams following a two-year retirement but didn’t make the trip to Australia for the opener.
The Rams enter Thursday’s game as 3.5-point favorites against the 49ers, returning a 2.56x payout if they win outright, via PrizePicks.
Here are the full payouts for the 49ers vs. Rams game on PrizePicks.
Make your 49ers vs. Rams prediction on the spread on PrizePicks.
PrizePicks data is live at the time of writing and is subject to change.
49ers vs. Rams Prediction on Spread for Week 1 – 9/10/26
Here are the key game stats and trends behind our 49ers vs. Rams prediction on the spread for Thursday, September 10.
- The Rams ranked first in offensive success rate (52.2%) last season, according to RBSDM.
- San Francisco’s defense ranked 25th in EPA/Pass and 29th in success rate (48.8%).
- Stafford’s MVP campaign was not only highlighted by a league-leading 4,707 passing yards but also by pacing the Rams to the second-best EPA/Pass rate.
- The Rams led the NFL in aDOT (average depth of target), while the 49ers ranked 20th.
- From a turnover standpoint, Los Angeles put together a +11 takeaway difference. San Francisco had only 6 INTs and finished -6 in the category.
- The 49ers have won four of their last five series openers, as they face the Rams in Week 1 for the first time since 2016.
- In pass rate over expectation via Establish the Run, the Rams ranked third at 3.3%, compared to -1.3 for the 49ers.
- From a luck standpoint, Los Angeles recovered 36.4% of its fumbles, while San Francisco picked up 45.5% of its fumbles.
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Make 49ers vs. Rams Picks on PrizePicks
It’s a long trip for both San Francisco and Los Angeles to Australia. The 49ers traveled a week ago, while the Rams headed down under the day before the game.
Will Los Angeles begin the season with a huge division victory, or can San Francisco pick up the underdog win in the first Thursday game of the 2026 NFL season?
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