Melvin Gordon matched a career high by scoring three touchdowns, and the Los Angeles Chargers defeated Buffalo 31-20 in manhandling the anemic Bills during rookie quarterback Josh Allen's debut as a starter.
Gordon scored on a 20-yard run and added two touchdowns receiving before limping off the field after appearing to hurt his left leg early in the fourth quarter.
The Chargers did not have an update on Gordon's status after he was evaluated in a tent on the sideline.
Gordon finished with just 28 yards rushing and six catches for 38 yards in his second three-TD game. He had two touchdowns rushing and one receiving in a 33-30 win at Atlanta on Oct. 23, 2016.
Rivers finished 23 of 27 for 256 and three touchdowns as the Chargers (1-1) rebounded from a 38-28 season-opening loss to Kansas City last weekend.
The Bills (0-2) also have a concern at running back after LeSean McCoy missed the entire fourth quarter with what the team called a rib injury.
McCoy was shaken up late in the third quarter when he was tackled from behind and had Buffalo center Ryan Groy fall down on him. Groy landed heavily on the left side of McCoy's chest as he was on the ground.
The Chargers took control in building a 28-3 lead with 1:55 left in the second quarter, when Rivers hit Gordon for a 2-yard touchdown pass. That capped a run in which Los Angeles scored touchdowns on four consecutive possessions.
Rivers began the run by hitting Mike Williams on a 10-yard pass 5½ minutes in. Gordon scored on a 20-yard run some five minutes later.
And then Rivers hit Gordon on a 9-yard touchdown pass to open the second quarter to cap a five-play, 75-yard drive, after the Bills scored on Stephen Hauschka's 43-yard field goal.
The Bills, in their home opener, got off to yet another miserable start a week after a 47-3 season-opening loss at Baltimore. Buffalo trailed the Chargers 28-6 at halftime and has been outscored by a combined 54-6 in the first half.
The Bills' latest meltdown featured cornerback Vontae Davis leaving the team at halftime. Davis explained his decision by saying he has decided to retire after 10 NFL seasons.
Allen did produce two touchdown drives in the second half, including a seven-play, 75 yard third-quarter-opening drive capped by Chris Ivory's 1-yard plunge.
Allen finished 18 of 33 for 245 yards with a 3-yard touchdown pass to Kelvin Benjamin with 38 seconds remaining, and two interceptions.
It was a modestly better showing at quarterback a week after Nathan Peterman was yanked after completing 5 of 18 attempts for 24 yards, with two interceptions, and overseeing an offense that managed just one first down over 10 series.
Whatever last chance the Bills had to get back into the game ended with about seven minutes left, when Allen threw his second interception. Facing first-and-11 at the Buffalo 2, Allen sailed a pass up the left sideline intended for tight end Jason Croom, but was picked off by leaping linebacker Kyzir White.
Los Angeles used up more than three minutes off the clock, sealing the win on Caleb Sturgis hitting a 24-yard field goal.