The Sabres, overcame a two-goal deficit in a bid to pull out what would have been a rare victory, but Michalek came through to bring the Senators their second straight win.
Buffalo's losing streak reached four games and the Sabres remained stuck on 15 victories, four fewer than any other team in the NHL.
Erik Karlsson's goal 3:12 into the middle period was the only goal for either team during the first two stanzas and Michalek gave Ottawa a 2-0 lead a mere 10 seconds into the third.
Michalek's game-winner came against Jhonas Enroth, who allowed the three goals on 36 shots. The win went to Craig Anderson, who made 30 saves.