Rams vs. 49ers Week 5 TNF: NFL Betting Odds & Picks

Last week we hit both of our TNF game bets but just missed by a few yards on our player prop. Of course the most consistent wideout in the league has a hiccup when we put down on him. As old Blue Eyes used to say though, that’s life.

In the Week 5 edition of Thursday Night Football, we get a second NFC West rivalry game in as many weeks, this one featuring the 3-1 Los Angeles Rams hosting the 3-1 San Francisco 49ers at SoFi Stadium. Will the Rams take advantage of the injury-plagued Niners and retain the top spot in the division? Or can a motley crew of San Francisco players pull an upset in L.A.? Read on for our picks as well as the best NFL betting odds!

2025 TNF Best Bets Record: 6-3 (+1.81)

Note: None of our best bets feature odds shorter than (-200).

NFL Week 5 TNF: Los Angeles Rams vs. San Francisco 49ers Betting Odds & Picks - Oct. 2

All odds provided by Sports Interaction.

Rams vs. 49ers Point Spread/Moneyline Prediction

After the onslaught of injuries the 49ers experienced last season, one would have thought they would have worn out all that bad injury karma. Not so. QB Brock Purdy, WRs Ricky Pearsall and Jauan Jennings, TE George Kittle, and of course edge Nick Bosa (the latter of whom is out for the season) will miss this game. At least they still have Christian McCaffrey (knock on wood).

The Rams got a bit lucky in their win over the Colts last week, but they got the win and they really should have beaten the Eagles as well. This is a talented football team, and as long as they can keep Matthew Stafford upright, they should win this game going away. And with Nick Bosa out and the 49ers putting up a 12.3 percent pressure rate, we think they definitely will.

Prediction: Los Angeles Rams -7.0 Point Spread (-110)

Rams vs. 49ers Over/Under Total Prediction

Each of the first three TNF games have hit 43 or more points. That’s pretty good for a series of broadcasts that has usually seen a lot of low-scoring affairs and sloppy play over the last few seasons. And while it’s been better this year, we’re do for an ugly one. And this one has ugly written all over it.

Mac Jones is capable enough. But without Jennings, without Pearsall, without Kittle. It’s just too much to ask him to overcome. The Rams have also been a top 10 defense and are tied for second in the league with 14 sacks. If they get Jones all flustered, this one could be over early, so we like the under this week.

Prediction: Game Total Points Under 45.5 (-110)

Rams vs. 49ers Player Prop Best Bets

On the 49ers side, we love Jake Tonges in this spot at 27.5 receiving yards. He’s been coming on stronger with each passing game, putting up a career-high last week with 58 yards on his five targets. In the two games Mac Jones has started this season, he had 21 and 31 yards. But that was with Pearsall and Jennings in the picture. He should get a ton more looks this week with those guys out and the 49ers playing from behind.

And speaking of playing from behind, if you prefer a Rams bet, Kyren Williams has a good number here with most Canadian sportsbooks giving us his rushing prop at 67.5. He has rushed for 66+ in each of his four games this season, and he should get a ton of work on Thursday night. The only worry here would be the Rams going up too much too early and Williams ceding the work to Blake Corum. Tonges is our favorite bet here, but Williams is also a good shout.

Best Bet:

• Jake Tonges Over 27.5 Receiving Yards (-110)
• Kyren Williams Over 67.5 Rushing Yards (-110)