James Harden made four three-pointers en route to 22 points off the bench for the Thunder, who have won five in a row against the Pistons and swept the home-and-home season series for the second straight year.
Serge Ibaka added 16 points and eight boards for Oklahoma City, which has won two straight and five of six overall. Russell Westbrook tallied 13 points and 11 assists.
Richard Hamilton finished with 20 points for the Pistons, who have lost 10 of their last 13 games.
Rodney Stuckey and Tayshaun Prince donated 16 and 15 points, respectively, for Detroit, which got 12 points and 10 rebounds from Greg Monroe. Tracy McGrady chipped in with 11 points and nine boards.