LaDainian Tomlinson carried 28 times for 110 yards and a touchdown, but the Chargers (8-6) wasted a chance to catch the Oakland Raiders (9-5) atop the AFC West, losing for the fifth time in seven games.
The Bills (7-7) had lost four of their previous five. They are mathematically alive for the postseason but need a lot of help.
Let go by Buffalo after the 2000 season, Flutie took his first snap of the year in the fourth quarter and led a 53-yard drive that culminated in a 53-yard field goal by Steve Christie -- another former Bill -- with 6:45 left.
Flutie, who was a cult figure during his three-year stint with the Bills, was greeted by a rousing ovation from the wind-chilled crowd of 61,838 at Ralph Wilson Stadium.
"It was fun to hear it from the crowd, step into a situation where we are behind and we have an opportunity to go out and win a ballgame," Flutie said. "Made a couple of plays, got us in position. Didn't follow through on it."
The Chargers went three-and-out on their next possession before Henry capped a 64-yard scoring drive with his second touchdown of the day. Henry carried 22 times for 144 yards as Buffalo overcame a 101-yard passing day by Drew Bledsoe.
"We have been talking about it a lot, that this team needs to rise up and play around Drew," Bills coach Gregg Williams said. "We shouldn't always have to lean on Drew. Our team needs to get better around him."
Bledose completed only 11 of 33 passes and finished with his worst yardage total since he threw for 101 against the Bills as a member of the New England Patriots on Dec. 26, 1999.
"They came in with a plan they were going to harass our guys, try and get an extra defender in the box and then try and harass our receivers outside," Bledsoe said.
Bledsoe still set his fourth single-season team passing record in his first year with the Bills, surpassing Hall of Famer Jim Kelly's mark for yards (3,844). Bledsoe now has 3,949.
"He's a hero of mine and anytime you can put your name up next to his, it's a positive thing," said Bledsoe, who also set records for consecutive passes without an interception (175), most yards in a game (463), fastest quarterback to 3,000 yards (10 games) and 300-yard games (7). "I'm proud of that."
Henry reached 100 yards for the sixthtime this season.
"I would hope I get the recognition," he said. "It's something that I work for, respect. Something I want people to know that I'm one of the top backs in this league, too."
Henry scored from four yards late in the first quarter to give the Bills a 7-3 lead. He had runs of 10 and 18 yards on the drive.
"I think their strategy was to put a lot of pressure on us and make us throw a lot," Bills wideout Eric Moulds said. "They had a great game plan coming in, but I think we were able to overcome it by the way Travis was able to run the ball."
Henry has 13 rushing touchdowns this season, three off O.J. Simpson's single-season team record. Cookie Gilchrist also had 13 in 1962.
The Chargers helped Buffalo's first touchdown drive with a pair of pass interference penalties. They were whistled four times for pass interference and totaled nine penalties for 121 yards.
"Defensively, we played well, except we had penalties, and you can't do that and be successful in this league," Coach Marty Schottenheimer said.
After Mike Hollis kicked a 41-yard field goal early in the second quarter, Tomlinson scored on a one-yard run with 3:21 left in the half to tie it at 10-10. The Bills took a 13-10 lead into the locker room following Hollis' 36-yard field goal.
The teams went scoreless in the third quarter as neither was able to move the ball through the gusts. Schottenheimer then decided to bench Brees for the more mobile Flutie.
"I felt in that scenario, in that situation, he'd be able to make plays by his movement," Schottenheimer said. "My decision to change quarterbacks will be driven by instinct as much as anything."
Brees, a second-year pro who had taken every snap since he was given the starting job in preseason, was 13 of 24 for 148 yards. Flutie went three of 11 for 64 yards.
"Doug went in and did a fine job," Brees said. "I know my job is secure. I'm not second-guessing myself, coach or anybody. I'm still very confident. Obviously upset about the loss."
Flutie took over with 8:23 to play and immediately threw a 47-yard completion over the middle to Curtis Conway, who juggled the ball three times before coming down with it. Four plays later, Christie kicked the tying field goal.
It was the longest kick in more than five years for Christie, who also was let go by the Bills after the 2000 season.