Harden hit 9 of 21 shots from the field, fellow guard Eric Gordon chipped in with 21 points, and center Clint Capela contributed 20 points and a team-high 17 rebounds.
It was the sixth consecutive victory for the Rockets (11-3), who led throughout.
Victor Oladipo led the Pacers (6-8) with 28 points on 11-of-17 shooting from the field.
Pacers forward Domantas Sabonis chipped in with 17 points, hitting 7 of 10 shots from the floor.
Lance Stephenson contributed a team-high 10 rebounds and eight points off the bench for the Pacers. Myles Turner scored 13 points and grabbed eight rebounds.
Harden scored 12 points in the third quarter as the Rockets expanded a 63-51 halftime lead to 87-71 after three.
The Rockets sank 43 of 90 shots from the field for 47.8 percent. The Pacers were 37 of 83 from the floor for 44.6 percent.
The Rockets had a 47-41 rebounding edge.
Gordon scored 15 points to help lift Houston to a 12-point halftime edge. Harden contributed 14 points and 11 rebounds in the first half.
Indiana sank 21 of 42 shots from the floor in the first half. Houston was slightly better, making 24 of 47 for 51.1 percent.
The Rockets had four more first-half 3-pointers with a 10-of-23 effort.
The Rockets, who jumped to an 18-4 lead, hit 14 of 24 shots from the field to take a 35-18 lead after one quarter.
NOTES: Rockets G Eric Gordon, from North Central High School in Indianapolis and a former Indiana University player, had scored 20-plus points in five consecutive games and in 11 of 13 overall this season. Gordon missed one game because of illness. ... Rockets G James Harden set the franchise record of starting the season with 20 or more points in the first 14 games. He had shared the record with Elvin Hayes (1979-70) of most consecutive 20-point games to start the season. ... Pacers F Thaddeus Young had scored in double figures in nine consecutive games but was held scoreless on 0-of-7 shooting from the floor. ... Pacers G Victor Oladipo has scored 20 or more points in 10 of 14 games this season. Oladipo has led Indiana in scoring 10 times.