Set to kick off Week 5 of the 2025 NFL season with a showdown between NFC West rivals, the San Francisco 49ers will travel to So-Fi Stadium to take on the Los Angeles Rams in a Thursday Night Football grudge match.
My best bet on Thursday Night Football Week 5 is to take the underdog 49ers to win against the Rams on the road.
49ers moneyline vs. Rams
+210
Thursday Night Football Best Bet: 49ers to Upset the Rams (+210)
Heading into a primetime clash that will decide who sits atop the NFC West, we can expect an intense atmosphere between these bitter rivals. While the Rams are off to their best start since the 2021 season, bank on the 49ers to pull off the upset on NFL Thursday Night Football.
Amidst yet another season chock-full of injuries, the 49ers have once again persevered, adjusted, and thrived under their given circumstances. Coming off a disappointing defeat to the Jacksonville Jaguars in Week 4, look for the Niners to bounce back in a big way as they remain perfect in divisional play.
While this matchup is sure to be closely contested, the upside of the 49ers will be too much for the Rams to handle. With the Rams defence set to struggle containing All-Pro running back Christian McCaffrey, as well as the dynamic passing ability of quarterback Brock Purdy, the 49ers will have no trouble putting points on the board.
At +210, these juicy NFL odds are too good to pass up on as the Niners are primed to come into the Rams’ barn, pull of the upset, and continue their quest towards their third NFC West title in four seasons.
49ers vs. Rams Betting Trends
- The Rams have won three straight head-to-head games against the Niners. The Rams haven’t won four games in a row since 2001, when they were still based in St. Louis.
- Through the first four weeks of play, the Rams are 3-0 against the spread as favourites. They’re currently slotted at -5.5 against the 49ers.
- In NFC West play this season, the 49ers have had both of their games finish under the projected total. The points total line for Thursday Night Football is set at 47.
- Not only have the 49ers been dominant on the road, having gone 2-0 as the visiting team, but they’ve also covered the spread in both of those matchups.
Top Player Props to Watch on Thursday Night Football
- WR Davante Adams Anytime TD Scorer (+130) – Three straight games with a touchdown.
- QB Matthew Stafford Over 239.5 Passing Yards (-110) – Hit in three of four starts this season, averages 278.5 passing yards per game.
- RB Christian McCaffrey Under 60.5 Rushing Yards (-110) – Three straight games with less than 61 rushing yards, averaging 56.25 rushing yards this season.
- QB Brock Purdy Over 1.5 Passing TDs (+125) – Has thrown two passing touchdowns in both games played in 2025.
Thursday Night Football Injury Report
49ers
- QB Brock Purdy (toe) – Questionable
- WR Ricky Pearsall (knee) – Questionable
- WR Jauan Jennings (ankle, rib) – Questionable
- DT CJ West (thumb) – Questionable
- WR Jordan Watkins (calf) – Questionable
- CB Renardo Green (neck) – Questionable
- LB Dee Winters (knee) – Questionable
- EDGE Mykel Williams (wrist, oblique) – Questionable
- EDGE Yetur Gross-Matos (knee) – Questionable
- EDGE Robert Beal (ankle) – Questionable
Rams
- T Rob Havenstein (ankle) – Questionable
- TE Tyler Higbee (hip) – Questionable
- S Kamren Kitchens (shoulder) – Questionable