It marks the third time in his seven NBA seasons that Durant has reached the 50-point plateau.
Durant established an NBA season high in scoring, besting his own 48-point performance put together on Jan. 7 against Utah.
The Oklahoma City superstar made 19-of-28 shots from the field and hit 5-of-9 from 3-point range. He also connected on 11-of-13 from the foul line and added five rebounds and six assists.
It took Durant's sensational effort to fight off Golden State, which shot 52 percent from the field compared with the Thunder's 58 percent.
Serge Ibaka added 21 points for Oklahoma City, which has won two straight to reach 30 victories for the season.
Stephen Curry scored 37 points for Golden State and Klay Thompson had 26.
Durant came into the contest leading the NBA in scoring with 30 points a game.