Usually known for his defense and energy, Ibaka dominated the post against Tim Duncan to help the NBA-leading Thunder (20-4) cruise to their 11th straight win.
"Serge was terrific tonight," Oklahoma City's Kevin Durant said. "They do a great job of taking the main scorers out of the game. So that's when you have to step up."
Russell Westbrook added 22 and nine assists while Durant added 19 for Oklahoma City in a rematch of last season's Western Conference Finals when the Thunder eliminated the Spurs.
The Thunder blew open a close game with an 11-0 run in the third quarter and used their speed and athleticism to run away from the Spurs.
Tony Parker had 14 points and seven assists for the visitors and Duncan was held to 12 but neither played in the fourth quarter where coach Gregg Popovich kept them on the bench with the game out of reach.
The Spurs were also without Manu Ginobili, who missed the game after sustaining a left quadriceps injury on Saturday against Boston.
The Spurs (19-7) have lost three of four and had their Southwest Division lead trimmed to one game.
Stephen Jackson returned to the court for the Spurs after missing 14 games with a broken finger.
Jackson had previously been fined $25,000 for a hostile Twitter message directed at Ibaka, but the Thunder forward hit back on the court where his offensive game continues to expand.
"He hurt us bad," Jackson said of Ibaka. "He had, what, 18 in the first half, 16 in the first half? He was hitting everything.
"That's the same way we lost last year in the playoffs, by him hitting those same shots. I take my hat off (to him)."
The Thunder lead the NBA in scoring and have not slowed down even after trading away Sixth Man of the Year James Harden in the off-season.
Kevin Martin, who they acquired in the deal, had 20 off the bench.