Detroit opened a 14-point lead after one period and held on, thanks to 24 points from Hamilton and 22 from Tayshaun Prince. They combined to make 18-of-33 from the field and Greg Monroe chipped in 21 points and 10 rebounds.
The Pistons won three of their four meetings with the Raptors this year.
Toronto lost for the fifth time in six outings and has dropped 14 consecutive road games. The Raptors last won on the road at Cleveland Jan. 5 and have just five victories away from home all season.
Andrea Bargnani scored 20 points for the Raptors and DeMar DeRozan had 16.