The 20-year-old French prodigy, a virtual certainty to be named the NBA's rookie of the year, was listed as out of Sunday's game against Detroit with a right ankle problem.
The announcement means Wembanyama's dazzling debut season in the NBA has come to a premature end, with his final act Friday's 34-point display in victory over the NBA champion Nuggets.
Wembanyama finished the campaign with an average of 21 points, 11 rebounds and four assists.
Wembanyama arrived in the NBA last year as the No. 1 pick in the Draft, with hype touting him as a generational talent on the level of LeBron James.
Although the Spurs suffered another losing season, and are currently bottom of the Western Conference, Wembanyama's eye-catching performances have wowed coaches, fellow players and fans.
On Friday, he led the Spurs as they overturned a 23-point second-half deficit to down the Nuggets in an upset that upended the Western Conference race for the No.1 seeding.
His performance included an incredible scoring blitz in the third quarter, where he rattled in 17 points in just three minutes.
"It just makes every win feel even more special," Wembanyama said after the win.
"As a growing team, a young team, it's big for us. We are going to need these kind of wins in the future."
