Dylan Cozens tied it up with his first of the year at 6:43, getting the puck all alone out front and trying to slip a backhand under Markstrom, the Flames 'tender stopping it but as he lay face down on the ice, he exposed the puck in the blue paint when he moved his legs and Cozens swept it across the line.
The Sabres went up 2-1 at 10:49 when Rasmus Dahlin skated in from the blueline as the trailer on a rush, firing it over the blocker of a screened Markstrom. The Buffalo blueliner has now scored in the opening four games of the season, becoming the first NHL blueliner to accomplish that feat.
Casey Mittelstadt added to the Buffalo run with a backhander on a shorthanded breakaway at 13:10.
Jonathan Huberdeau, Dillon Dube and Mikael Backlund had great chances in the final three minutes of the frame but couldn't find the twine.
Alex Tuch beat Vladar him shortside 46 seconds into the middle stanza to make 4-1.
Tage Thompson stepped into a howitzer of a one-timer on the powerplay with 13:06 to go in period and the refs called it a goal but after review, they overturned as it went off the post and out of harm's way.
Lewis made it a two-goal gap when he tallied with 1.6 seconds left in the second, grabbing the loose puck after Huberdeau lost the handle and putting into a yawning cage.