The Sabres not only squandered a lead entering the third period for the first time this season, but also lost leading scorer Thomas Vanek, who didn't return after he hurt his left foot in the first period.
Chara and Ryder both scored twice for the Bruins, who erased deficits of 2-0 and 3-2. Chara broke a 3-3 tie by snapping in a shot from the left point that floated over the right shoulder of Ryan Miller, who was screened by David Krejci with 12:37 left.
Jason Pominville, Matt Ellis and rookie defenseman Tyler Myers scored for Buffalo.
Game 3 is Monday night in Boston.
Mark Recchi sealed the victory by scoring into an open net as the Bruins ended a seven-game playoff losing streak at Buffalo. The drought spanned four series, dating to a 5-4 overtime win in the first round in 1992.
The Sabres regained momentum with 3:19 left in the second period when Tyler Ennis set up Pominville in front to put Buffalo ahead 3-2. But Buffalo couldn't hold on in the decisive final 20 minutes.
The Sabres were 30-0 in the regular season when entering the third period with the lead. The were the first to have an unblemished record since Chicago went 19-0 during the 1994-95 regular season.
The Bruins turned the game their way by recording the first seven shots of the third and scoring twice.
Ryder tied it at 5:23. The Bruins capitalized on a transition break after the Sabres failed to get a shot on goal during a 3-on-2 rush. The Bruins came back on a 4-on-2 break.
Andrew Ference drove with the puck into the slot, drawing Miller's attention. Ference slipped a pass to his left, and Ryder swept a shot into the open side.
Chara's go-ahead goal came after Sabres center Tim Connolly coughed up the puck in his zone. The puck dribbled directly to the Bruins captain, who immediately snapped it on net.
The Sabres came out flat, and didn't get their first shot of the third period until 10:15 had elapsed, when Pominville fired a drive from the right circle on a power play.
Vanek, a top-line forward, was injured after he was hooked from behind by Johnny Boychuk during a partial breakaway with under seven minutes left in the first. After getting off a backhand shot, Vanek and Boychuk both fell and slid into the end boards.
Vanek had difficulty putting weight on his left foot as he attempted to get up. He hobbled to the Sabres bench and fell to his knees as he tried to get through the gate. The Sabres said Vanek had an undisclosed lower body injury and wouldn't return.
The injury is potentially a serious blow to Buffalo. A two-time 40-goal-scorer, Vanek led the Sabres with 28 goals in the regular season. He scored five goals in Buffalo's final two games after missing six games because of a groin injury.
Vanek also scored a goal in Game 1 and assisted on Myers' opening tally Saturday.
The Sabres built a 2-0 by the 12-minute mark of the first on goals by Myers and Ennis.
The Bruins got even at 2 when Ryder and Chara scored 7:19 apart in the second period.
Notes
Bruins assistant coach Craig Ramsay was back behind the bench after missing Game 1 and spending Thursday night in a Buffalo hospital because of the flu. … The Sabres are 32-7-4 this season when scoring the first goal, including both games of this series. … Buffalo is already missing two top forwards. Jochen Hecht will be out at least two weeks (pinkie surgery), and Drew Stafford (concussion) is day to day.