Brunson was one of four Knicks to finish in double figures, with Karl-Anthony Towns adding 18 points, OG Anunoby 17 and Landry Shamet 13.
Wembanyama led San Antonio’s scoring with 26 points but had a poor shooting night, making just 6-of-21 from the field while pulling down 12 rebounds with three blocks.
“I was bad tonight, it’s not more complicated than that,” said Wembanyama, who denied nerves had been a factor in the Spurs defeat.
“It definitely felt special for sure, but nothing close that could be an excuse,” Wembanyama said. “It was not a factor in our performance.”
Stephon Castle had 17 points and Dylan Harper and Julian Champagnie added 16 points apiece.
An absorbing first half saw the Knicks make a bright start to take a 14-7 lead before San Antonio hit their stride with a 9-0 run to claim their first lead of the game at 16-14.
A pair of three-pointers from Champagnie helped the Spurs suddenly accelerate into a 10-point lead with two minutes remaining in the first quarter.
The Knicks were then given a huge scare in the final two minutes of the first when Brunson left the game with a worrying-looking knee injury sustained after a collision with San Antonio’s Harrison Barnes.
Brunson returned to the game in the second quarter, and although there was another injury scare when he appeared to hurt an ankle after a layup, he remained in the game to play the decisive role.