In a pivotal matchup with massive NFC West ramifications, Garoppolo will look to lead San Francisco past the defending Super Bowl champions in a primetime Monday Night Football bout. Can Stafford and Cooper Kupp pull off the win and move to 3-1? Or will the 49ers squeeze a win out Los Angeles? The game kicks off Sunday at 8:15 p.m. from Levi's Stadium.
Here's a look at the betting details and USA TODAY's NFL staff picks for the Rams vs. 49ers Week 4 game:
Rams at 49ers odds, moneyline and over/under
Spread: 49ers (-1.5)
Moneyline: 49ers (-125); Rams (+105)
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NFL Week 4 odds, predictions and picks
Dolphins vs. Bengals | Vikings vs. Saints | Browns vs. Falcons | Seahawks vs. Lions | Jaguars vs. Eagles | Commanders vs. Cowboys | Titans vs. Colts | Jets vs. Steelers | Bills vs. Ravens | Chargers vs. Texans | Bears vs. Giants | Cardinals vs. Panthers | Patriots vs. Packers | Broncos vs. Raiders | Chiefs vs. Buccaneers | Rams vs. 49ers
Lorenzo Reyes: Rams 25, 49ers 17
So that’s why the Niners wanted to move from Jimmy G. While Sean McVay and Kyle Shanahan know each other very well, the loss of Trent Williams spells trouble for an offense that lacks an identity. And the Rams simply have the better roster — even with a banged-up secondary.
Safid Deen: 49ers 23, Rams 20
The Rams have gotten back on track with wins over Atlanta and Arizona, but no team has been a bigger thorn in their side in recent years than the 49ers. The Rams were able to beat the 49ers in the NFC title game last season to end a six-game skid against their in-state rivals. And San Francisco would love nothing more than to avenge that loss. 49ers coach Kyle Shanahan has always found a way to get the best of Rams coach Sean McVay, and this is a prime opportunity for Jimmy Garoppolo and his teammates to get back on the winning side of this series and improve to 2-2 this season.
Lance Pugmire: Rams 24, 49ers 17
The returning champions are yearning to pronounce the legitimacy of their defense, and there’s no better opportunity than to do so against their bitter rival in the Bay Area.
Jarrett Bell: Rams 23, 49ers 16
Nate Davis: 49ers 27, Rams 24
Tyler Dragon: Rams 27, 49ers 20
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This article originally appeared on USA TODAY: Los Angeles Rams at San Francisco 49ers: Game odds, picks, predictions