Wilcox finished with 13 points and 12 rebounds for the Pistons, who trailed by 11 in the opening minute of the fourth quarter.
"I thought in that fourth period being down eight we made some adjustments," said Detroit head coach John Kuester. "Will Bynum did a phenomenal job. In fact, our bench had 54 points. They did a great job of distributing the basketball and making big shots."
Amare Stoudemire totaled 20 points and 12 boards to pace the Knicks, who were coming off Thursday's win over Memphis. Toney Douglas, who hit nine of New York's 20 three-pointers against the Grizzlies, ended Friday's game with 20 points and 11 assists.
Carmelo Anthony had only six points after missing 10 of his 12 shots, contributing to New York's fourth loss in five games.
"It is disappointing anytime you lose," said New York head coach Mike D'Antoni. "Tonight we had 18 turnovers that gave them 28 points and on the road you cant turn the ball over like that."
Shawne Williams' three-pointer 29 seconds into the fourth quarter gave New York an 81-70 advantage, but the Knicks missed their next three shots as Detroit ran off five consecutive points.
After Stoudemire got a jumper to fall, the Pistons pulled even. Ben Gordon drove for a layup, and Villanueva canned back-to-back threes, making it an 83-83 game with eight minutes left.
Both teams led down the stretch, and New York held a 95-93 edge with two minutes to go. Chauncey Billups' missed three-pointer set up a Pistons fastbreak, which Rodney Stuckey finished with a layup with 88 seconds remaining.
Another Williams miss gave the ball back to Detroit, and while Bynum couldn't get a layup to drop in, Wilcox was there to slam home the rebound.
Anthony's potential game-tying layup was off the mark at the other end, and the Pistons drained some time off the clock before Bynum missed a jumper. Prince grabbed the critical rebound, and Bynum made two game-securing free throws with 11 seconds left.
While neither team had tremendous offensive success in the closing minutes, New York didn't make a field goal after Douglas' layup with 3:13 to go.
Detroit held a 26-25 edge after the first quarter and a 55-53 lead at halftime. But the Pistons shot only 29 percent in the third quarter, as New York moved in front.
Stuckey finished with 12 points for Detroit...New York attempted only 11 free throws, making nine...The Knicks' 18 turnovers led to 28 Pistons points...New York had won the first two meetings this season.