49ers vs. Rams Predictions, Picks & Best Bets for Thursday Night Football

The Los Angeles Rams will host the San Francisco 49ers in a key NFC West clash on Thursday Night Football, October 2, 2025. Los Angeles enters as a strong 8.5-point favorite against a depleted San Francisco roster. Backup quarterback Mac Jones will start for the 49ers, who are without several offensive playmakers.

This primetime matchup marks a test for the Rams, who have won three straight against the 49ers after previously struggling in the rivalry. With injuries reshaping San Francisco’s game plan, Los Angeles looks ready to extend its winning streak at home.

Game Outlook and Expert Predictions

The Rams’ offense remains among the NFC’s best. Quarterback Matthew Stafford has found consistency with wide receivers Puka Nacua and Davante Adams, while running back Kyren Williams keeps defenses honest. Los Angeles also boasts one of the league’s top-ranked defenses, capable of pressuring quarterbacks and limiting explosive plays.

The 49ers, meanwhile, will be without key starters Brock Purdy, Brandon Aiyuk, George Kittle, and Jauan Jennings. Head coach Kyle Shanahan is expected to lean heavily on star running back Christian McCaffrey. However, Los Angeles’ defense ranks near the top against the run and will likely stack the box to contain him.

Analysts expect the Rams to control the game early. Pete Truszkowski and other betting experts recommend Rams -8.5 as a spread pick, with some also leaning toward the total going under 44 points due to San Francisco’s offensive limitations. Davante Adams is highlighted as a strong anytime touchdown scorer because of his red-zone target share.

Another popular prop bet is linebacker Byron Young to record a sack. Young has started the season with five sacks in four games and will face an injury-weakened 49ers offensive line. Bettors also like Puka Nacua to go over 7.5 receptions, given his consistent high target volume.

Impact for NFC West and Season Momentum

This game could shape early NFC West standings. A Rams win would strengthen their case as division frontrunners and add pressure to a 49ers team already battling injuries. San Francisco began the year 3-0 but now faces adversity, while Los Angeles remains unbeaten at home in 2025.

The matchup also has fantasy football implications. Nacua and Adams are must-starts in most formats. McCaffrey will remain heavily involved but could see limited efficiency against an elite Rams run defense. Bettors and fantasy managers alike are watching how Mac Jones performs under pressure in a hostile environment.

With the Rams healthy and explosive on offense, and the 49ers struggling to field their top players, Los Angeles appears primed to win comfortably. The game will likely hinge on whether San Francisco’s defense can slow down Stafford and force turnovers.

FYI (keeping you in the loop)-

Q1: Who is starting at quarterback for the 49ers tonight?

Mac Jones will start for the 49ers as Brock Purdy remains sidelined with injury.

Q2: What is the Rams’ current winning streak against San Francisco?

The Rams have won three straight games against the 49ers heading into this matchup.

Q3: What are the top betting picks for this game?

Rams -8.5, under 44 total points, Davante Adams anytime touchdown, Puka Nacua over 7.5 receptions, and Byron Young to record a sack.

Q4: Can the 49ers win with Mac Jones at quarterback?

It’s possible but challenging. Jones has played well in two starts, but Los Angeles’ strong defense and home advantage make it an uphill battle.

Q5: What time does the 49ers vs. Rams game start?

Kickoff is scheduled for 8:15 p.m. Eastern Time on Thursday, October 2, 2025.