Holding a 3-2 lead with only 36 seconds remaining, it appeared the Blue Jackets (0-7-1) would wrap up their first victory of the season.
But it wasn't to be as the Senators pulled their goalie to add an attacker and Spezza notched the equalizer after a scramble in front of the net.
Michalek then redirected a Sergei Gonchar shot from the point past Columbus goalie Steve Mason with only 5 seconds left in regulation, stunning the Blue Jackets and handing Ottawa a second straight win for the first time this season.
Craig Anderson stopped 18-of-21 shots to earn the victory.
Notable deaths of 2014 [PHOTOS]