Harden and Westbrook each donated 24 points for the Thunder, who are off to the franchise's best start (14-3) since the Seattle SuperSonics opened 14-3 in 2004-05. Durant added 20 points.
Oklahoma City, which shot 53.2 percent from the field, improved to 7-1 at home this season.
Brandon Knight ended with 13 points for the Pistons, who have lost 15 straight to Western Conference opponents on the road since a 100-94 triumph over Sacramento in November 2010.
Stuckey started the game with a jumper, but from that point on it was all Thunder. Holding an 11-8 edge with 7:44 to go, Oklahoma City closed the half on an 18-4 run. Harden had seven points during the burst to help give the home team a 29-12 lead after 12 minutes.
Oklahoma City shot 57.1 percent from the field in the first quarter, while limiting the Pistons to 16.7 percent shooting.
The Thunder continued to roll early in the second, scoring 10 of the period's first 12 points. Harden's three-pointer made it a 39-14 contest with 9:53 remaining.
Oklahoma City's margin grew to 56-24 on Westbrook's layup with 4 1/2 minutes left. It was a 60-33 game at the break, and the Thunder cruised to victory in the second half.