Ginobili scored a team-high 34 points and had seven assists, but the Spurs lost 108-106. They now trail the Thunder 3-2 in the best-of-seven series.
Ginobili replaced Danny Green, who entered Monday shooting just 8 of 28 in the Western Conference finals. It was the first start for Ginobili since March 23 and just his eighth all season.
Spurs coach Gregg Popovich wouldn't discuss any lineup changes before the game. But the move was a big shake-up for the Spurs after they dropped Games 3 and 4 in Oklahoma City following a 20-game winning streak.
Ginobili entered Monday averaging 13.1 points in the playoffs.
Information from The Associated Press was used in this report.