De’Aaron Fox hit the game-winner after enduring a tough series so far, as the Spurs avoided falling 3-0, which no NBA team has ever come back from.
They have a chance to tie the series on Wednesday night and are guaranteed another game at home.
Jalen Brunson scored 32 points, and OG Anunoby had 28 for the Knicks, who lost for the first time since April 23 in Game 3 of their first-round series against Atlanta.
Wembanyama, whose turnover late in Game 2 practically cost them, bounced back in style at MSG.
He had 10 points in the final quarter, helping the Spurs build a comfortable lead.
The 22-year-old finished with 32 points and should have had more after a four-point play was controversially chalked off.