SANTA CLARA, Calif. (Interstat) — Matthew Stafford passed for 280 yards and four touchdowns, and the Los Angeles Rams avenged an early-season overtime loss by dominating the San Francisco 49ers 42-26 on Sunday at Levi’s Stadium.

The Rams (7-2) seized control immediately, scoring touchdowns on their first three possessions to build a 21-0 lead and never looked back in front of a crowd of 71,239. The victory snapped a two-game winning streak for the 49ers (6-4) in the NFC West rivalry and handed San Francisco a costly divisional loss.

Stafford was surgical, completing 24 of 36 passes and spreading the wealth. He connected with Kyren Williams, Davante Adams, Puka Nacua, Davis Allen, and Colby Parkinson for scores. Williams was a dual threat, rushing for 73 yards and two touchdowns while also catching a scoring pass.

Los Angeles set the tone from the opening kickoff. A 28-yard return by Blake Corum set up a commanding 10-play, 85-yard drive capped by a 2-yard touchdown run from Williams. After forcing a quick punt, the Rams needed just six plays to find the end zone again, with Stafford hitting Nacua for a 22-yard score to make it 14-0.

The Rams’ defense stifled the 49ers’ offense for the entire first half outside of one drive. San Francisco quarterback Mac Jones, who finished 33 of 39 for 319 yards and three touchdowns, finally got the home team on the board with a 6-yard pass to Jauan Jennings late in the second quarter.

Any momentum for San Francisco was short-lived. The Rams opened the second half with another methodical touchdown drive, this one culminating in Stafford’s 2-yard pass to Adams to extend the lead to 28-7.

San Francisco showed signs of life in the fourth quarter. Jones led a 14-play, 85-yard drive that ended with a 9-yard touchdown pass to Luke Farrell, though the extra point was blocked. After the Rams answered with Williams’ second rushing touchdown, Jones engineered another scoring drive, finding George Kittle for a 13-yard touchdown. A failed two-point conversion attempt left the score at 42-26 with just under three minutes to play.

The 49ers’ attempted onside kick was recovered by the Rams’ Parkinson, allowing Los Angeles to run out the clock and seal the victory.

Despite the prolific passing numbers from Jones, the 49ers’ ground game was largely ineffective. Christian McCaffrey was held to 30 yards on 12 carries, though he added 66 receiving yards. Kittle led all receivers with nine catches for 84 yards and a touchdown.

Defensively, the Rams were led by a trio of players with 11 tackles each: linebackers Nate Landman and Omar Speights, and safety Quentin Lake. For the 49ers, safety Ji’Ayir Brown and linebacker Tatum Bethune each recorded 10 tackles in a losing effort.

The Rams’ win, coupled with their loss to the 49ers in overtime on Oct. 2, splits the season series and gives Los Angeles a critical head-to-head tiebreaker advantage. The result defied pregame expectations, as San Francisco had been installed as a 5.5-point favorite, and the combined 68 points sailed over the projected over/under line of 49.5.