Mark Scheifele scored three times, including twice in the third period, and set up another goal to pace the Colts offensively. Scheifele's second goal, on the power play midway through the third period, tied the game at three.
Josh MacDonald's power play goal at 17:14 of the third put the Colts ahead to stay.
Jared McCann, Michael Schumacher and Ryan Sproul scored for the Greyhounds in the loss.
Goaltender Matt Murray stopped 34 shots.
Along with Scheifele's big performance, Anthony Camara had a goal and an assist in the win. Aaron Ekblad and Zach Hall added two assists each in the win while goaltender Mathias Niederberger stopped 30 shots.
The Greyhounds return to action on Wednesday night when they host the Sudbury Wolves at the Essar Centre. Game time is 7:07 p.m.