The Rockets (47-23) have won four of five.
Indiana's sinking playoff hopes took another big hit despite 23 points from C.J. Watson.
George Hill had 20 points for the Pacers (30-40).
It looked as though Houston would run away after jumping to an early double-digit lead and extending the margin to 41-20 early in the second quarter.
Indiana finally rallied in the third, using a 16-4 spurt to get as close as 68-66 in the final two minutes.
But the Rockets closed the quarter on an 8-2 run to take a 76-68 lead. They rebuilt a double-digit margin early in the fourth, and then Harden sealed the win by scoring 12 points in a four-minute flurry.
For Harden, it was another big night against Indiana's usually staunch defense. He nearly matched his 45-point effort in the first game of the season series by going 10 of 21 from the field and 21 for 22 from the free throw line with seven assists and four rebounds.
Boston 110, at Brooklyn 91:
Memphis 103, at New York 82:
at Chicago 98, Charlotte 86: Nikola Mirotic scored 14 of his 28 points in the fourth quarter, and the
Minnesota 106, at Utah 104 (OT): Rookie guard