Andrew Shaw had a goal and an assist for the Blackhawks, who earned their fifth consecutive win against the Sabres. Brandon Saad had a career-high three assists and Corey Crawford made 21 saves.
Zemgus Girgensons and Tyler Ennis scored in the first period for Buffalo, which lost 3-1 to Columbus in its season opener on Thursday night. Drew Stafford had two assists and Jhonas Enroth had 41 stops.
The Sabres and Blackhawks were tied at 2 before Kane one-timed a backhand pass from Shaw past Enroth at 5:58 of the third. It was the first of the season for the Buffalo native, who has five career goals against his hometown team.
Chicago poured it on from there. Hossa had a short-handed score at 10:03, Sharp converted a long power-play slap shot and Daniel Carcillo tapped in a feed from Saad with 2:37 left in the game.
Coming off a 3-2 shootout win at Dallas in their season opener, a victory that coach Joel Quenneville said they stole from the Stars, the Blackhawks jumped out to a fast start in their first meaningful home game since they lost to the Stanley Cup champion Kings in Game 7 of an epic Western Conference final.
Shaw tipped Niklas Hjalmarsson's long shot past Enroth just 59 seconds into the game. Duncan Keith then had another long shot go off the stick of a Sabres player and into the upper right corner for a 2-0 lead at 2:52 of the first.
With the crowd of 22,012 looking for a quick knockout, Enroth settled down and the Sabres went to work on Crawford. Girgensons poked home a rebound to get Buffalo on the board, and Ennis scored on a short-handed breakaway to make it 2-2 at 18:40.
Stafford set up the tying score when he intercepted a pass from Brad Richards near the blue line and played it forward to a streaking Ennis, who skated in on Crawford for his first goal of the season. The Blackhawks went 1 for 4 on the power play.
Chicago had a chance to go in front in the final seconds of the first, but Enroth made a great save on Jonathan Toews right in front of the net.
Buffalo had the best opportunity in the scoreless second period. After Blackhawks defenseman David Rundblad failed to control the puck at the point, Nicolas Deslauriers got loose for a breakaway, but was stopped by Crawford, leading to chants of ''Co-rey! Co-rey!'' from the crowd.
NOTES: The Flames scratched C Brian Flynn and Ds Tyson Strachan and Nikita Zadorov. ... F Kris Versteeg and Ds Kyle Cumiskey and Michal Rozsival were the scratches for the Blackhawks ... Former Chicago Bears quarterback Jim McMahon received a standing ovation before he participated in the shoot the puck contest in between the second and third periods.