Harden returned to Oklahoma City for the first time since being traded just before the season and it was a forgettable night for him and the Rockets (7-8).
Powered by Durant's hot shooting, the Thunder (12-4) blew open a close game in the second quarter where they led by 18 before keeping the visiting Rockets at bay.
"I really wanted to win this game," Durant said. "Especially for all those times in practice that (Harden) and the rest of the second team beat all of us on the first team."
Serge Ibaka backed Durant with 23 and nine rebounds and Oklahoma City raced to their second straight blowout, having destroyed Charlotte 114-69 on Monday.
Harden, the Sixth Man of the Year last season, has emerged as the lead scorer for Houston but struggled against the Thunder making three of 16 shots for 17 points.
It had already been a humbling day for the Rockets who earlier attended the funeral of coach Kevin McHale's daughter who died from an auto-immune disease last week. McHale has been away from the team since November 10.
Patrick Patterson scored a team-high 27 points for Houston but there were few bright spots for the visitors.
The Rockets were within two after the first quarter, but Oklahoma City opened the second with a 9-0 run and kicked things into another gear.
Kevin Martin, who was sent to the Thunder from Houston as part of the Harden trade, ended up with 17 points off the bench.
Harden got a warm ovation from the fans prior to the game. His quick departure had come as a shock to basketball fans after he helped lead Oklahoma City to the NBA Finals but could not come to terms on a new contract with the team.
"I was put in a tough situation where things didn't happen the way I wanted them to," Harden said. "That's in the past. All I can do now is focus on what I need to do to be a better basketball player and leader."