3 Key Matchups for Rams vs. San Francisco 49ers

The Los Angeles Rams will need to be successful in these three key matchups of the game vs. the 49ers on Thursday night.

Sep 28, 2025; Inglewood, California, USA; Los Angeles Rams quarterback Matthew Stafford (9) leaves the field after the game against the Indianapolis Colts at SoFi Stadium. Mandatory Credit: Jayne Kamin-Oncea-Imagn Images | Jayne Kamin-Oncea-Imagn Images

Tomorrow begins the battle for the NFC West title as the Los Angeles Rams and San Francisco 49ers will tango at SoFi Stadium on Thursday night. This is the Rams' first divisional matchup of the season as they look to get back to their winning streak ways with a 4-1 start to the year following slower intiations to previous years.

With this matchup in over 24 hours, we take a closer look at a few of the key matchups for Thursday night. This could be a physical, tough game with 49ers defensive coordinator Robert Saleh going toe to toe with Rams head coach and play-caller Sean McVay, and both teams offering the talent and temperament to make this a wire-to-wire game.

Los Angeles Rams defensive line vs. San Francisco 49ers offensive line

Sep 28, 2025; Inglewood, California, USA; Los Angeles Rams linebacker Jared Verse (8) forces a fumble by Indianapolis Colts quarterback Daniel Jones (17) in the fourth quarter at SoFi Stadium. Mandatory Credit: Jayne Kamin-Oncea-Imagn Images | Jayne Kamin-Oncea-Imagn Images

With a big question mark on a short week with the 49ers quarterback situation, the Rams' defensive front is firing on all cylinders to begin the season. Byron Young is off to an incredible start with five sacks in four games and is looking to add his sixth or seventh on Thursday night. Jared Verse is beginning to heat up as well, early in the campaign, with Kobie Turner, Braden Fiske, Poona Ford and Tyler Davis rotating in the middle.

The 49ers are 11th in pressure rate and seventh in pressures allowed overall. It has not been a great start for this front as they face another strong defense in back-to-back weeks. Left tackle Trent Williams will be key to this unit's success, especially for their star running back.

Los Angeles Rams defense vs. Christian McCaffrey

Sep 28, 2025; Santa Clara, California, USA; San Francisco 49ers running back Christian McCaffrey (23) carries the ball against the Jacksonville Jaguars during the second quarter at Levi's Stadium. Mandatory Credit: Darren Yamashita-Imagn Images | Darren Yamashita-Imagn Images

For my money, Christian McCaffrey is one of the best pure offensive playmakers in the sport, maybe a better player than Saquon Barkley when healthy. Week in and out, he provides so many different challenges in both the run game and the passing game. The Rams have the 10th-best rushing defense in yards per game this season, but McCaffrey's skill set is broader than that.

It will take all 11 players on defense to defend McCaffrey, whether it be out of the backfield, on the perimeter, or in the slot. The man they call "CMC" will be one of the Rams' biggest challenges early this season, providing a major test for defensive coordinator Chris Shula.

Matthew Stafford vs. San Francisco 49ers

Sep 28, 2025; Inglewood, California, USA; Los Angeles Rams quarterback Matthew Stafford (9) throws against the Indianapolis Colts during the second half at SoFi Stadium. Mandatory Credit: Gary A. Vasquez-Imagn Images | Gary A. Vasquez-Imagn Images

Stafford is a fantastic quarterback, and he was when it mattered most last weekend in the 27-20 victory over the Indianapolis Colts. Even at age 37, the Rams signal-caller is one of the best in the league and remains such a threat with his incredible arm talent. Now, he faces maybe the second or third-best defense he'll play this season.

Saleh is a terrific defensive coordinator, and he showed last week that he can compensate well without star pass rusher Nick Bosa. Linebacker Fred Warner will remain a challenge, as will cornerback Deommodore Lenoir and a young secondary and defensive unit overall. In what is expected to be a physical game, look for Stafford to be the difference with his arm, throwing toward wide receivers Puka Nacua, Davante Adams, and Tutu Atwell.

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