San Francisco 49ers vs Los Angeles Rams Prediction 9/10/2026 Today’s NFL Picks

The San Francisco 49ers and the Los Angeles Rams meet in week 4 NFL action from Melbourne Cricket Grounds on Thursday. We will look at this from a betting perspective and determine the best bets for this game. Here’s a San Francisco 49ers vs. Los Angeles Rams prediction.

San Francisco 49ers Team Preview

The San Francisco 49ers enter the 2026 season looking to make another deep postseason run under Kyle Shanahan following a 12-5 campaign in 2025 that ended in the Divisional Round with a thud in a 41-6 loss to Seattle. In 2025, Christian McCaffrey led the offense with 1,202 rushing yards and 10 touchdowns, George Kittle added 628 receiving yards, and Brock Purdy threw for 2,167 yards and 20 touchdowns, while Dee Winters posted 101 tackles and Nick Bosa anchored the defensive line. During the 2026 offseason, general manager John Lynch retooled the receiving core by signing Mike Evans and bringing back Deebo Samuel Sr., while trading for defensive lineman Osa Odighizuwa to strengthen the interior front. In the draft, San Francisco selected Washington State target De’Zhaun Stribling in the second round to add immediate depth to the passing attack. Backed by an established foundation of Purdy, McCaffrey, and Bosa, the 49ers head into 2026 aiming to capture the NFC West title and make a return trip to the Super Bowl.

Los Angeles Rams Team Preview

The Los Angeles Rams enter the 2026 season looking to build on a strong 12-5 campaign in 2025 under Sean McVay that saw them reach the NFC Championship Game before a 31-27 loss to the Seattle Seahawks. In 2025, Matthew Stafford led the Rams under center, an offense that scored a league-best 518 points, while Kyren Williams 1,252 rushing yards and Puka Nacua’s 1,715 receiving yards were the straw that stirred the drink. During the 2026 offseason, general manager Les Snead aggressively upgraded the secondary by trading for Trent McDuffie and signing Jaylen Watson, while also adding linebacker Grant Stuard. In the draft, the Rams selected Alabama quarterback Ty Simpson in the first round as a long-term option behind Stafford. Backed by a revamped secondary alongside an elite core featuring Stafford, Williams, and Nacua, the Rams head into 2026 primed to challenge for the NFC West crown and contend for a Super Bowl.

San Francisco 49ers @ Los Angeles Rams Betting Trends: Week 1

Why the Los Angeles Rams will win

• The Rams have won each of their last eight September games as favorites.
• The 49ers have lost each of their last four games without Christian McCaffrey.
• The Rams have covered the spread in each of their last six season openers as favorites.
• The 49ers have failed to cover the spread in each of their last five games without Deebo Samuel.
• The Rams have scored the first touchdown in 10 of their last 13 games as favorites.
• The Rams have won the first quarter in each of their last four season openers against NFC opponents.
• The favorites have won the first half in each of the 49ers’ last 12 games.

Why the San Francisco 49ers will win

• The underdogs have won four of the last five games between the 49ers and Rams.
• The Rams have lost five of their last six September games against NFC opponents.
• The 49ers have covered the spread in eight of their last nine games as underdogs against the Rams.
• The Rams have failed to cover the spread in five of their last six September games against NFC opponents.
• The 49ers have scored the first touchdown in five of their last six Week 1 games.
• The 49ers have won the first quarter in each of their last three September games as underdogs.
• The 49ers have won the first half in five of their last six season openers.

Total Points Facts

• Each of the last seven games between teams from the same division have gone OVER the total points line.
• Each of the Rams’ last six games at neutral venues have gone UNDER the total points line.
• Nine of the 49ers’ last 10 season openers against NFC opponents have gone UNDER the total points line.

Los Angeles Rams Player Prop Facts

• Kyren Williams has scored two or more touchdowns in four of his five previous appearances against the 49ers.
• Colby Parkinson has recorded 21+ receiving yards in each of the Rams’ last 10 games.
• Kyren Williams has recorded 57+ rushing yards in each of the Rams’ last seven games as favorites.
• Kyren Williams has recorded 72+ rushing and receiving yards in each of his last 10 regular season appearances against NFC West opponents.
• Matthew Stafford has recorded 24+ completions in eight of his last 10 Week 1 appearances.
• Matthew Stafford has recorded 286+ passing yards in 12 of his last 15 Week 1 appearances.
• Kyren Williams has scored at least one touchdown in each of the Rams’ last seven September games against NFC opponents.
• Matthew Stafford ranked 1st in the NFL in passing yards (4707) last season.

San Francisco 49ers Player Prop Facts

• Deebo Samuel has scored at least one touchdown in each of his last four appearances with the 49ers as underdogs against NFC West opponents.
• Brock Purdy has recorded 21+ rushing yards in each of the 49ers’ last four games.
• Brock Purdy has recorded 277+ passing yards in each of his last five September appearances.
• Deebo Samuel has recorded 41+ receiving yards in each of his last seven appearances with his team as an underdog against NFC West opponents.
• Brock Purdy has recorded 22+ completions in each of his last four September appearances against NFC opponents.
• Deebo Samuel has recorded 44+ rushing and receiving yards in each of his last 11 September appearances against NFC opponents.
• Brock Purdy recorded the equal-most passing touchdowns in a single game last season (5 vs Colts, Week 16).

Matchup/League Facts

• Rams – two different players recorded 80+ rushing yards in a game last season – equal-most in the NFL.
• Rams – two different players recorded 90+ rushing yards in a game last season – equal-most in the NFL.
• The 49ers ranked 32nd in the NFL in sacks (20.0) last season.
• The 49ers ranked 32nd in the NFL in total punt yards (1919) last season.

San Francisco 49ers vs. Los Angeles Rams Prediction

I’m on the Rams in this one. I get the case to be made for the 49ers as historically, this has been a head-to-head matchup where betting on the underdog has worked out well. However, this is a matchup that’s also turned on it’s head in recent years, with the Rams owning a lot of the head-to-head meetings as of late. I know a lot of focus may be on this new revamped Rams unit, but I think in the end, the Rams still have the better pieces to get it done here so give me the Rams.

Chris Ruffolo's Pick: Los Angeles -3.5