John-Michael Liles produced a power-play goal 57 seconds into the middle period to give the Maple Leafs a 2-1 lead, but the Bruins then turned up the heat while snapping a two-game skid.
Seguin tied it with a slap shot and Chris Kelly put Boston in front 39 seconds later.
Phil Kessel brought Toronto back into a tie midway through the second with his 33rd of the season, but goals by Jordan Caron and Seguin late in the stanza put the Bruins in control.
Mikhail Grabovski brought the Maple Leafs within one with 6:47 to play in regulation, but Thomas held on and finished with 25 saves.
All five Boston goals came against Jonas Gustavsson on 33 shots.