Guerin took a feed from Doug Weight near the Sabres' net and knocked in his team-leading 15th goal of the season 1:35 into overtime.
It was the Blues' season-high third straight win of the season. St. Louis hadn't won three in a row since February.
Guerin tied the game at two midway through the third period, tipping Jay McClement's blast past Buffalo goaltender Martin Biron seconds after the Sabres killed off a St. Louis power-play. Teppo Numminen left the penalty box following his two-minute minor for interference but barely got back on the ice before Guerin scored.
The Sabres seemed to take a 3-1 lead on Jochen Hecht's second goal of the game early in the third period. However, the referees reviewed the play and waived off the goal, claiming Hecht kicked the puck into the net.