Harden's 48-point heroics mean he and the legendary Wilt Chamberlain are the only players in history to score 30-plus points in 19 consecutive games, Sky Sports reported.
The Lakers, again missing LeBron James through injury, wasted an 18-point lead when the Rockets' Eric Gordon scored a three-pointer with two seconds remaining to force overtime. From there, Harden took over.
The Rockets led the game for the first time in the opening period of overtime.
Reigning MVP Harden finished with 14-for-30 shooting from the field, 8-for-19 from three-point range and 12-for-15 from the three throw line. He has scored 40-plus points in 11 games this season.
Gordon, as well as scoring the vital three-pointer to wipe out the Lakers' lead, totaled 30 points.
For the Lakers, Kyle Kuzma shone with 32 points and Brandon Ingram scored 11 in overtime, 21 overall.
But Lonzo Ball sustained an ankle injury that ended his participation and head coach Luke Walton was ejected.
Walton had said in the buildup that his Lakers needed to stop Harden from completing a third consecutive 50-point game. They achieved that, by two points, but Harden still had the final say.