49ers vs. Rams betting preview: Odds, picks, props, trends, injuries, weather and more for Week 5 Thursday Night Football

The NFC West has the Thursday Night Football spotlight to itself on Prime Video for the second week in a row as the 49ers (3-1) visit the Rams (3-1) to kick off Week 5. Los Angeles hasn't had much of a home-field advantage when hosting San Francisco in recent years at SoFi Stadium as it's usually a sea of red, but the Rams are -8.5 with a total of 45. Both numbers have shifted a fair amount due to significant Niners injuries.

Home teams are 3-1 SU and 1-3 ATS on Thursdays in 2025 after Arizona lost and failed to cover in the desert last week against Seattle. The NFC West could be the most intriguing division race of the year as all four teams are legitimately capable of winning it and all four are quite flawed. The Rams are +115 favorites and the Niners are +180, and they play again in Santa Clara in Week 10. 

Los Angeles is 3-1 for the first time since winning the Super Bowl in 2021 when the team started 7-1. Sean McVay's club logged a remarkable win Sunday over previously unbeaten Indianapolis, 27-20. Matthew Stafford hit Tutu Atwell on an 88-yard touchdown pass with 1:33 left, the longest game-winning offensive TD in league history in the final two minutes of the fourth quarter. That's bonkers. It also marked the third-longest game-winning TD of any kind in the final two minutes of the fourth since 1960.  

San Francisco is seeking its third 4-1 or better start under coach Kyle Shanahan (5-0 in 2019 and 2023). The Niners are 2-0 on the road after going 2-6 in 2024 and are 2-0 vs. the NFC West after finishing 1-5 a year ago. San Francisco is succeeding despite some major early offensive injuries to QB Brock Purdy, WR Jauan Jennings and TE George Kittle, as well as averaging a scant 3.3 yards per carry. Shanahan has blamed the issues on a lack of explosive runs as the team doesn't have a run for more than 20 yards yet. Christian McCaffrey's longest this season is 15 yards, and he has yet to even reach 70 in a game.

We'll take you through every aspect of the 49ers vs. Rams game that you need to know before you lock in your bets, including SportsLine expert picks, props, trends, DFS, injury information and everything else that will help you know which plays are worth making for the primetime matchup.

Who wins 49ers vs. Rams in the Week 5 Thursday night game, and what critical X-factor makes one side of the spread hit HARD? Join SportsLine right now to see everything you need to know to dominate your Thursday Night Football bets, plus get expert picks, model sims, prop bets, DFS lineups, and more!