The Penguins (10-7-3) are 12-0-1 against the Sabres (5-9-4) since a 4-1 loss on April 2, 2013.
After Crosby tied it 3-3 on a power play with 2:45 remaining in the second period, Benoit Pouliot scored a power-play goal to give Buffalo a 4-3 lead with 6.7 seconds left in the period. The goal was Pouliot's sixth of the season, all in the past 10 games.
Crosby ended his 11-game drought by collecting a rebound off a shot from Kessel and shooting past Lehner. He hadn't scored since Oct. 20, in a 4-3 win against the Florida Panthers.
The drought ended one game shy of Crosby's NHL career high of 12, from Nov. 23, 2011, to March 22, 2012.
"You're happy to see it go in the net," Crosby said. "There were some good chances. I think as long as they're there, hopefully they'll start to go in a little bit more."
Jack Eichel ended a drought of his own when he scored for the first time in nine games to give the Sabres a 3-1 lead 16 seconds into the second period. Crosby turned the puck over behind the Pittsburgh net, which led to Eichel backhanding a shot around the right post for his first goal since Oct. 21, in a 5-4 win against the Boston Bruins.