The Rockets built a 15-point lead early in the fourth quarter and easily held on for the win. Houston has captured three out of four during a stretch in which they will play five of six on the road.
Harden, the NBA's fifth leading scorer, hit half of his 14 attempts from the field while the Rockets were shooting 53 percent as a team. Six Houston players reached double figures in scoring.
Brook Lopez had 27 points for the Nets, who missed a chance to climb into a tie with New York for the Atlantic Division lead.
Houston went into the game holding down the eighth spot in the Western Conference playoff race.