Buffalo, which saw its first two-game win streak under first-year coach Dick Jauron come to an abrupt end, fell behind 17-0 in the first half and wound up being out-gained 335-230 in yardage by San Diego's high-powered offense.
But despite a brief rally when the Bills capitalized on several Chargers miscues and erupted for 14 points in a 6:51 span of the third quarter, they could not pull off the upset.
The Chargers (10-2), who put themselves in great position to earn home field advantage throughout the AFC playoffs on a day when Indianapolis (10-2) lost to Tennessee, sealed the victory with a 13-play, 80-yard drive that chewed up 8:06 of the fourth quarter and upped their lead to 24-14.
Only a late Buffalo scoring drive capped by J.P. Losman's six-yard pass to Peerless Price in garbage time made the score close.
The Bills (5-7) travel to New York next to take on a resurgent 7-5 Jets team.
"The integrity of our game is based on effort and these are quality guys and they'll play," said Jauron. "The playoffs are still there and we're not mathematically eliminated that I'm aware of. Even if we were, they'll still play hard."
The Bills have fallen to division-leading New England twice, Chicago, Indianapolis and San Diego. Those games include losses by two points to the Patriots, one to the Colts and three to the Chargers. But a loss is still a loss.
"We knew in camp we had a good team, we just haven't had that last little bit to win these big game," defensive tackle Larry Tripplett said. "We still need that last little step to get over the hump. It's going to come. I promise you."
Despite being the cold-weather team, Buffalo couldn't run the ball or stop the run with any efficiency against San Diego.
Led by MVP candidate LaDainian Tomlinson on offense and linebacker Shawne Merriman, who returned to the lineup after serving a four-game suspension for violating the NFL's substance abuse policy, on defense, San Diego held a decisive 197-63 edge in yards on the ground.
Tomlinson gained 178 yards on 28 carries and scored two touchdowns, giving him 26 on the year, just two shy of the NFL single-season mark. Merriman dominated all in his path with two sacks, two forced fumbles and a tipped pass.
Buffalo took advantage of a team sack that forced a Rivers' fumble on the opening series of the third quarter. Set up at the Chargers' 19-yard line, Losman needed just four plays to find Robert Royal open on a five-yard touchdown play.
After Buffalo's defense forced a quick three-and-out, highlighted by Ryan Denney's sack of Rivers, a short punt into the wind was returned 32 yards by Jim Leonhard to the San Diego 13-yard line.
From there, four Bills running plays, including a two-yard plunge by Willis McGahee, produced another quick TD to cut San Diego's lead to 17-14.
But it was San Diego's 13-play drive that snuffed out Buffalo's upset bid. Rivers went four-for-four passing, including two big completions to Gates for 19 and 10 yards. Tomlinson did the rest, scoring his second TD on a two-yard run off left tackle without being touched.
"We've had a couple of games now where we couldn't get off the field on that last drive," rookie strong safety Donte Whitner said. "We just have to stay in our gaps and play sound defense, but on that last drive, we didn't really do that."