Bouncing back from a home-court upset loss on Monday, the Western Conference second-seeded Spurs' resounding win reestablishes them as favourites to progress.
Seven-foot-four (2.24m) phenom Wembanyama was in imperious form again in San Antonio, with 19 points plus 15 rebounds and two blocks, as the Spurs notched up their highest playoff score since 1983.
The newly crowned NBA defensive player of the year also helped restrict Minnesota to just 35 points in the first half -- the Timberwolves' lowest-scoring half all season -- to ensure the vital series-tying win was essentially decided by the break.
"I'm expecting this kind of response from myself, from my teammates, so I'm not surprised by any means," said Wembanyama.
"There is some ego. They assaulted us in game one, we wanted to assault in game two," the Frenchman added.
Minnesota's 24-point halftime deficit only widened in the second half, peaking at 47 points, before San Antonio rested its starters for the final stages.
The performance came after Minnesota's head coach had accused Wembanyama of repeated illegal goaltending violations in game one, during which the Frenchman had made a playoff record 12 blocks.
Asked if there had been any anger on his part entering game two, he replied: "There always is. In the playoffs, magnify that."
Minnesota ace Anthony Edwards, who shone in game one after returning from a left knee injury, was restricted to 12 points and spent the final quarter on the bench icing his legs.
The two sides meet again on Friday in Minneapolis for game three.