Detroit stayed perfect at 3-0 with a road win on Sunday night.
Cade Cunningham scored 26 points, with eight rebounds and seven assists.
The Pistons jumped to a 15-1 lead and never trailed in the game.
Detroit built a 21-point lead late in the second quarter.
Duncan Robinson scored 21 points to back up Cunningham.
Tyrese Maxey scored 29 points after a slow start for the 76ers.
LeBron James scored 18 points in his return from a one-game absence.
Philadelphia cut the gap to four points late, but Detroit held firm.
Joel Embiid rested to manage a painful foot problem, despite wanting to play.
Adem Bona grabbed 13 rebounds and blocked three shots for Philadelphia.
Philadelphia visits the Pacers on Wednesday to chase a bounce-back win.
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