The world number one had won 11 of 12 previous meetings against the veteran Czech, and he improved that record with a 6-2 6-4 victory in Toronto.
Djokovic put Stepanek under pressure from the outset, turning it into a comfortable win after one hour, 28 minutes.
With his win, the three-time champion set up a quarter-final meeting with Tomas Berdych.
Djokovic broke twice in the opening set, taking a 4-1 lead before closing it out on the back of 20 unforced errors from Stepanek.
The players traded breaks in the second before Djokovic saw out victory in the 10th game, an outrageous lob on match point sealing his win.