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Brandon Aiyuk of the San Francisco 49ers catches a touchdown against Patrick Peterson of the Pittsburgh Steelers at Acrisure Stadium on Sept. 10, 2023 in Pittsburgh, Pennsylvania as we share our favorite 49ers vs. Rams prediction.
Brandon Aiyuk of the San Francisco 49ers catches a touchdown against Patrick Peterson of the Pittsburgh Steelers at Acrisure Stadium on Sept. 10, 2023 in Pittsburgh, Pennsylvania. Photo by Joe Sargent/Getty Images via AFP.

Here are our top predictions for the 49ers vs. Rams, all based on the best NFL odds from our best sports betting apps. While the San Francisco 49ers have often held the upper hand over the Los Angeles Rams in recent seasons, the Rams have the opportunity to reverse the trend this Sunday.

The San Francisco 49ers have rolled off eight consecutive regular-season wins over the Los Angeles Rams, and even in challenging years like 2020, the 49ers managed to top their division rivals.

Expectations were low for the 2023 Rams, but LA surprised with an impressive 30-13 road win against the Seattle Seahawks last week. Quarterback Matt Stafford aired it out for 334 passing yards, and rookie wide receiver Puka Nacua made history by becoming the fifth player in the last 60 years to record 10 or more receptions in his NFL debut.

To complement your NFL best bets for Week 2NFL upset picks and NFL player props here is our best 49ers vs. Rams prediction (odds via our best NFL betting sites; pick confidence based on a 1-to-5-star scale).

49ers vs. Rams prediction

Over 44.5 points (-115 via FanDuel) ⭐⭐⭐⭐

As good as the Rams’ win was in Seattle last week, the Seahawks’ defense is not as strong as San Francisco’s. The Niners’ D led the league last season in points allowed and was tied for second in takeaways. Despite new defensive coordinator Steve Wilkes, they don’t appear to have changed much in 2023.

Second-year defensive end Drake Jackson rung up three sacks in Week 1, while the defense held the Pittsburgh Steelers to just 3.9 yards per play with a 33% third-down conversion rate and kept Pittsburgh QB Kenny Pickett to a 68.4 QB rating. That was even without defensive end Nick Bosa being fully reintegrated with his team.

The 49ers rushed for 150-plus yards in six straight regular-season games, tied for the team's second-longest streak. But, as McVay and the rest of the NFL know, Shanahan’s offense is a juggernaut. They punish opponents on the ground and through the air. Niners QB Brock Purdy threw two touchdown passes to wide receiver Brandon Aiyuk in San Francisco's  30-7 victory at Pittsburgh last Sunday. Purdy is the first QB in NFL history to win each of his first six career regular-season starts and throw at least two touchdown passes in each.

Wide receivers Tutu Atwell and Nacua each had 119 receiving yards in the Rams’ win in Seattle. If there's a weak spot for the 49ers' defense, it's against slot receivers. Cooper Kupp, unavailable for this game, averaged 110.25 receiving yards per game in his last four meetings with San Francisco, so McVay knows how to move the ball against them.

It's a divisional matchup that averaged 42.5 points per game over the last four regular season meetings. With Shanahan’s offense firing on all cylinders, take the Over.  

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49ers vs. Rams best odds

FanDuel -115

Over 45 pointsOver 44.5pointsOver 45.5 pointsOver 45.5 pointsOver 45.5 points

The total opened at 43.5 and dropped as low as 42.5 Monday. Since late Monday afternoon it's hovered around 44.5 and 45. Both teams had 30 points last Sunday, and although the Rams will find it tougher to score against San Francisco’s defense, McVay should have something schemed up.

The line had considerable movement Friday, with three of our best sports betting apps moving it up from 44.5 to 45.5. FanDuel is the only book to drop its line, although the odds increased to -115. Take fewer yards to ensure the win. This is a total very much in your grasp.

49ers vs. Rams odds

49ers vs. Rams odds analysis

The Rams are huge underdogs at home in a divisional matchup. They’re +7 ATS with some of our best sports betting sitesFanDuel has the best odds for the spread at -110.

There’s little value in betting the 49ers on the moneyline at -320. The odds dropped significantly overnight Thursday, with the public favoring San Francisco. If you think L.A. can cause an upset, the moneyline odds are +270, up from +240 on Thursday.

Purdy is -110 to throw over 1.5 touchdown passes against the Rams. Stafford is +134 for the same play.

49ers vs. Rams game info

  • When: Sunday, Sept. 17 at 4:05 p.m. ET
  • Where: SoFi Stadium, Inglewood, CA
  • How to watch: Fox
  • Weather: Indoors

49ers-Rams prediction made 9/15/23 at 3:05 p.m. ET

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