DeJuan Blair added 18 points and 12 rebounds for San Antonio, which improved its NBA-best record to 43-8. Manu Ginobili scored 13 points for the Spurs, and Tim Duncan contributed 10 points and 10 rebounds.
Will Bynum scored 12 of his 21 points in the fourth quarter for Detroit (19-33).
San Antonio had set a record for the franchise's best 50-game start, but the Spurs struggled to pull away from the Pistons. Their lead didn't reach double figures until the final minute.
Blair's double-double was his second in a row and seventh since Jan. 1.
Bynum made a dunk and a 15-footer to pull the Pistons within two at 80-78 in the fourth, but Ginobili and Matt Bonner made back-to-back 3-pointers. Bonner returned after missing 10 games with a right knee injury and scored 10 points — eight of them in the fourth quarter.
Another 3-pointer by Ginobili made it 89-80.
In a matchup of promising young big men who used to play at Big East schools, Pittsburgh's Blair got the better of Georgetown's Greg Monroe, but not by much. Monroe had 14 points and 13 rebounds for the Pistons.
Richard Jefferson scored 11 points for the Spurs, whose balance proved to be too much for Detroit. All five starters scored in double figures for San Antonio, which become only the fourth opponent to score 100 points in Detroit's last 14 games.
One game after returning from an extended benching, Detroit's Richard Hamilton sat out Tuesday night's matchup because of a sore right groin. Hamilton scored 15 points in 20 minutes Saturday at Milwaukee, his first action since Jan. 10 after he was benched and even deactivated for Friday night's home game against New Jersey.
A few players returned from injuries Tuesday. In addition to Bonner, Detroit guard Rodney Stuckey returned after missing five games with a right shoulder injury. Stuckey didn't start but finished 10 points on 4-of-12 shooting.
Detroit's Jason Maxiell, who has been bothered by a back problem, scored two points in his first appearance in four games. It was the first time Maxiell played more than a minute since Jan. 22.
Notes: Detroit plays at Cleveland on Wednesday night, with the Cavaliers trying to snap their record streak of 25 losses. ... San Antonio signed F Steve Novak to a 10-day contract before the game. Coach Gregg Popovich said Novak's job is to shoot when he goes into the game. Novak played 45 seconds on Tuesday, which was enough time for him to make a 3-pointer. ... San Antonio shot 53 percent but turned the ball over 14 times. Parker alone had six turnovers, as many as the entire Detroit team.