NFL: Rams vs 49ers Predictions and Odds - Monday Night Football Preview

The NFC West favorites have gotten off to shaky starts. But we are in for a treat if the game is anything like last year’s meetings!

Rams vs 49ers Predictions: Recommended Bets

Monday Night Football Game: Are you ready for some football?

As a follow-up to last week’s NFC East slugfest between the New York Giants and Dallas Cowboys, we get another MNF rivalry game! On Monday, October 3, at 8 p.m. Eastern Time (coverage starts at 7 p.m. on ESPN), the Rams-49ers rivalry will again take over our living rooms!

The Rams and 49ers, who last met with a trip to the Super Bowl on the line, square off in an NFC West clash vital to both teams. In our Rams vs 49ers predictions, there is quite a bit of history. This is why the Rams vs 49ers odds are so tight. 

The Rams lost the first two meetings last year against the 49ers and, in the NFC Championship, looked destined for a third defeat. However, with the team trailing 17-7, Matthew Stafford led the Rams to three fourth-quarter scoring drives (totaling 13 points) to put the team ahead and allowed the defense, which held the 49ers scoreless in that period, to punch their ticket for the Super Bowl.


Point spread



Los Angeles Rams

+1.5 (-107)

O44.0 (-107)


San Francisco 49ers

-1.5 (-107)

U44.0 (-107)


Odds taken from: PointsBet (Accurate as of 09/30/22)

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Rams Are The Underdog Monday

It’s tough to believe the Rams vs 49ers odds could include a Super Bowl defending champion getting plus-money, but here we are, with the Rams as 1.5-point Monday night underdogs. Part of that is history, and part of that is that the game is being played in San Francisco (Santa Clara, actually, but you get the point). Typically, the unwritten rule is a home team gets three more points for being at home. 

In case you’ve forgotten, those three meetings in 2021 went a little like this: The Niners blew out the Rams on a Week 10 Monday night in northern California by a 31-10. Then, in L.A. in Week 18, they got past the Rams 27-24 in overtime to close out the regular season. 

These Rams vs 49ers predictions do take into account that the Rams have bounced back since being routed by the Buffalo Bills by  21 points in Week 1 and have held on to defeat the Atlanta Falcons 31-27 at home (admittedly not the most confidence-inspiring of results) and shut down the Arizona Cardinals in a 20-12 win. 

The Rams are still trying to get Matthew Stafford healthy while sorting out their running game. Last week, they stifled the Arizona offense, forcing Kyler Murray to throw the ball a whopping 58 times and holding the running game to just 70 yards on 21 carries, and limited the Cards, again, to just 12 points. This raises our hopes in the Rams vs 49ers predictions because if that Super Bowl caliber defense is truly back, then the 49ers may also have serious difficulties scoring this week.

The questions on the offensive side of the ball are still there as Matthew Stafford and Cooper Kupp have been rolling well this year, though Kupp was held to four catches for just 44 yards last week.

San Francisco Relying On Jimmy Garoppolo For Better or Worse

Despite all that went on last season in San Francisco, the 49ers were still one drive away from going to the Super Bowl. The Rams vs 49ers predictions could never have guessed an offseason where it looked like Jimmy Garoppolo was all but gone and then had to come back due to a shoulder surgery torpedoing his trade value. That shoulder surgery, as it turns out, was a blessing.

This is because Trey Lance, the #3 overall pick in the 2021 NFL draft and starter to begin the 2022 season, only made it to Week 2 before a gruesome ankle injury (a broken bone and two torn ligaments) ended his season. Jimmy G came on in relief, led the 49ers to an easy victory, and all that was old was new.

That was the “good” for Garoppolo, Deebo Samuel, and the offense. The “bad” came last week in Denver, when the 49ers could only manage 10 points and fell to the Broncos, 11-10, in a game that was every bit as ugly as the score would suggest. This is often the problem for San Francisco. Their defense keeps in games, but too often, the offense cannot generate enough to deliver victory. That is why the Rams vs 49ers odds are where they are. It’s also why making Rams vs 49ers predictions can get pretty infuriating. 

San Francisco averages 15.5 points per game in 2022 but yields just 12.3 a contest. The good and the bad with the Jimmy Garoppolo offense are crystal clear as we dig further into the Rams vs 49ers predictions.

Frequently Asked Questions (FAQs)

What time is the Rams vs 49ers game?

The 49ers will host the Rams at 8:15 pm EST on Monday, October 3. The game is on ESPN.

Who is the 49ers quarterback?

San Francisco’s starting QB ahead of Week 4 is Jimmy Garoppolo. The 49ers began the season with Trey Lance at quarterback. However, after Lance suffered a season-ending injury in Week 2, Garoppolo became the starter in Week 3.



Given the close Rams vs 49ers odds for Monday night’s game, this is not an easy game to predict. The two teams usually play close contests, and Los Angeles has more to play for. After all, San Francisco can get rolling at any time. Even at 3-5 last year, they made the playoffs. The Rams want to make sure that does not happen again.

Meanwhile, the Rams' defense showed its teeth last week in shutting down Kyler Murray and the Cardinals. This could be the perfect springboard for L.A., and the outcomes of these teams’ two non-overtimes last season offer something to sink our teeth into in the Rams vs 49ers predictions. In those contests, these two teams combined for an average of 39 points per game. This is likely similar to the type of game we’ll see on Monday. 

The likeliest outcome on Monday night is a victory for the Rams (at +115 in the Rams vs 49ers odds) over the narrowly-favored Niners. Another glance at our Rams vs 49ers odds also suggests that under 44 points is a likely outcome.

One of the biggest things we learned in Week 3 of the NFL is to keep expecting the unexpected.

Who are you backing in the Rams vs 49ers predictions? Interested in more NFL content? Read our guide: How to bet on NFL, and visit our odds comparison tool to compare the latest odds.


Written by Chris Wassel.

Chris is an experienced sports betting writer who loves sports irrationally. He has covered everything from the NFL, NHL to NASCAR to March Madness, including a couple of Stanley Cups, several NHL Drafts, and award shows.   

He is a veteran writer with over 30 years of fantasy hockey experience, contributing to several sports books and countless publications such as USA Today, The Hockey News, and Sportsnet.