It was only the second loss of the season for the Spurs, who had won 11 consecutive games. Oklahoma City picked up its fifth straight victory.
Durant scored 13 of his 24 points during the second half and was particularly effective while the Thunder outscored San Antonio 25-15 in the third period.
Serge Ibaka had 13 of his 17 points in the second half to keep Oklahoma City unbeaten at home. Reggie Jackson equaled his career best with 23 points.
The Spurs were led by 16 points and seven assists from Tony Parker.