It was the first meeting between the teams since the Flyers eliminated the Sabres in seven games during their Eastern Conference quarterfinal last season.
Sean Couturier, James van Riemsdyk and Scott Hartnell scored for the Flyers, who won their second straight after losing four of five.
Luke Adam had a goal and an assist and Andrej Sekera also scored for the Sabres, who have lost four of five. They fell to 1-4-0 in Buffalo.