James also had nine rebounds and seven assists for Cleveland (9-4).
Danny Granger had 19 points and nine rebounds, and Dahntay Jones added 17 points for the Pacers (5-5), who lost their second in a row.
Cleveland center Shaquille O'Neal missed his fourth straight game with a strained right shoulder. He did not travel with the team, and Cleveland coach Mike Brown didn't give a timetable for his return.
Pacers coach Jim O'Brien was thrown out of the game with 5:20 left in the first quarter after drawing two technical fouls for walking out to near midcourt to argue with officials.
The Pacers shot 63 percent in the first half, but 32 in the second. Indiana shot 24 percent in the second half of a loss to New York on Wednesday.
James made his first eight shots and didn't miss a field goal until the final three minutes of the second quarter. He finished the first half with 22 points and five assists as Cleveland led 66-61 at the break. The Pacers shot 63 percent in the first half, yet trailed because they were outscored 15-8 from the free throw line.
Indiana took its first lead, 70-68, when James was called for goaltending on a shot by Roy Hibbert with just over eight minutes left in the third quarter. It was part of a 17-2 run at the start of the second half that gave Indiana a 78-68 lead. Cleveland shot 3 for 18 from the field with seven turnovers in the quarter, and the Pacers led 82-77 at the end of the period.
Cleveland tied the game at 82 on a 3-pointer by Jamario Moon early in the fourth quarter, and the game was competitive until the final minutes. James sucked the life out of the Pacers and sent the crowd to the exits with a 3-pointer over Jones as the shot clock expired that gave the Cavaliers a 101-94 lead with 53 seconds left.
