Monday Night Football Predictions Week 10 | MNF Picks & Rams vs 49ers Best Bets

Last Updated: Nov 15, 2021

Heading into Week 10, there is suddenly a very important NFC West matchup in primetime.

Both the Rams and 49ers lost in Week 9, despite being home favorites. Now, the Rams desperately need a win to keep pace with the Arizona Cardinals in the division and the 49ers need a victory to stay competitive in the NFC Wild Card hunt.

Who will emerge victorious in this NFC West battle on Monday Night Football? Let’s dive into the odds and give our picks.

Please note that all Rams vs 49ers odds and lines are current as of 2 PM EST on Friday, November 12.

Sportsbook Play of the Day

Before reading our Monday Night Football betting tips, you should know that FanDuel is one of our favorite sportsbooks for NFL betting. FanDuel is offering an exclusive 30/1 odds boost on this week’s Rams vs 49ers game for new signups.

Read Chris Wassel’s FanDuel Sportsbook review to learn more about FanDuel and get an even bigger welcome bonus below, or continue reading this analysis for our Rams vs 49ers tipster picks.

Monday Night Football Prediction Week 10

The 49ers look like a team in disarray right now. San Francisco had a perfect opportunity to get back on the right track in Week 9 when it hosted an Arizona Cardinals team without Kyler Murray or DeAndre Hopkins. But instead, the 49ers were blown out in a game that was never really competitive.

Unfortunately, this is becoming a little bit of a trend as they have now lost five of their last six games with their only win coming against the Bears and rookie quarterback Justin Fields. The defense just isn’t good enough and the secondary is among the worst in the NFL.

Look for Matthew Stafford and the Rams’ offense to get back on the right track on Monday night as they should be able to score more than 30 points in San Francisco. This is a game that has a chance to be non-competitive right away given the talent differential at quarterback and in the secondaries for both teams.

MNF Week 10 NFL Prediction: Rams 31, 49ers 20

Cooper Kupp, WR Los Angeles Rams

Rams wide receiver Cooper Kupp will look to have another big game on MNF after already racking up over 1,000 receiving yards and 10 touchdowns in the team’s first nine games. (Image: USA TODAY Sports)

Monday Night Football Best Bets Week 10

MNF Best Bet: Rams -3.5 (-112) at TwinSpires

Wager: 1 Unit

The Rams did not look good on Sunday Night Football as they were dominated by the Tennessee Titans. However, they are still one of the best teams in the NFL. Their offense is as dangerous as any in the league and the 49ers just don’t have the secondary to slow down Cooper Kupp, Robert Woods, and the recently-acquired Odell Beckham Jr..

The 49ers have now allowed 202 points in eight games this season and have the No. 25-ranked scoring defense in the NFL. San Francisco’s defense has regressed so much since its run to the Super Bowl back in 2019.

The 49ers are the home team in this one and it is always a little bit concerning to give away 4.5 points to a road team, but the Rams are just the far better team and should have no problem scoring points at will in this game.

Take the Rams to win and cover in Week 10 as they should put on a show on offense in this game.

MNF Best Bet: Over 49.5 Total Points (-108) at TwinSpires

Wager: 1 Unit

Despite their performance on Sunday Night Football against the Titans, the Rams still have one of the league’s best offenses. Los Angeles is averaging 29 points per game and that number was significantly higher before Week 9.

With the 49ers being decimated in the secondary with injuries, it would be a shock if the Rams didn’t score at least 30 points in this game.

Can the 49ers get to 20 or more points in this game? Probably. They are going to need to throw more than usual and that should lead to points.

This one will be close, but take the Over to hit in San Francisco as both offenses should be able to move the ball up and down the field.

Thanks for reading our NFL Week 10 MNF Predictions! For more betting analysis, check out our NFL Week 10 Best Bets!


Marcus Mosher

Marcus Mosher is an NFL analyst at The Game Day, residing in Erie, PA. He covers the NFL from a betting and fantasy perspective, producing written and video content. Marcus currently hosts multiple football-related podcasts and is a managing editor at USA Today’s Sports Media Group covering the Las Vegas Raiders. He has previously worked at The Athletic and Bleacher Report.

Related articles


Get $1,500 in Bonus Bets

5 stars

Bet $5, Get $150 in Bonus Bets or First Bet Safety Net

5 stars

$1,500 No Sweat Bet + NBA SGP Token

5 stars

Get A Bonus Bet Up to $1,000

5 stars

Bet $5, Get $150 in Bonus Bets

5 stars

Get Up To $250 Second Chance Bonus Bet

5 stars

If you or someone you know has a gambling problem and wants help, please call 1-800-GAMBLER.

21+ and present in OH. Gambling Problem? Call or text 1-800-GAMBLER (CO, DC, IL, IN, LA, MD, MS, NJ, OH, PA, TN, VA, WV, WY).

Call 877-8-HOPENY or text HOPENY (467369) (NY).

Please Gamble Responsibly. Call 1-800-NEXT-STEP (AZ), 1-800-522-4700 (KS, NV), 1-800-327-5050 (MA), 1-800-BETS-OFF (IA), 1-800-270-7117 for confidential help (MI).

All betting content on is exclusively intended for audience members 21 years and older who are permitted to gamble in legal states. The Game Day may earn revenue from site visitor referrals to betting services.

Responsible Gaming: Many sportsbooks offer ways to encourage responsible gaming, including the establishment of limits to deposits, spending, and time dedicated to betting.

The Game Day is a TGD Marketing Ltd. endeavor.