Marreese Speights scored 18 points and Tristan Thompson added 16 for Cleveland, which scored 13 straight points in a stretch that began late in the third period to take control of the game.
The Cavaliers scored the last eight points of the third quarter to go ahead 85-80. A basket by Shaun Livingston and a 3-pointer by Wayne Ellington put Cleveland ahead 90-80 early in the fourth. The Cavaliers scored 34 points in the final period.
Nikola Vucevic scored a career-high 25 points for Orlando, which has lost 23 of 25. Arron Afflalo added 23 points and rookie Andrew Nicholson scored 21, but it wasn't enough for the Magic, who haven't won since Jan. 16.
Speights, who was 12 for 12 at the foul line, scored 12 points in the stretch that helped Cleveland take over. The Cavaliers, who tied a season high with their third straight victory, have won six of eight.
The win snapped Cleveland's 10-game losing streak against Orlando. The Cavaliers hadn't beaten the Magic since a 115-106 win on Feb. 11, 2010. Cleveland fell 108-104 in Orlando in November, a game Irving missed with a broken finger.
Cleveland's star point guard, who will compete in the All-Star game, the 3-point contest and the Rising Stars Challenge next weekend in Houston, scored seven points in the fourth quarter.
The game was tied at 24-24 after one quarter and again at 56-all at halftime. Cleveland has won six of seven at home.
The Magic had 11 players in uniform. Afflalo played for the first time since Jan. 27. He missed six games, four with a calf injury and two for personal reasons J.J. Redick (sore right shoulder) missed his third straight game while Hedo Turkoglu (flu) sat out his second straight game.
Orlando hadn't lost 12 straight games since a 13-game run March 13-April 10, 2004. The latest defeat tied the Magic with Washington for the second-longest losing streak of the season in the NBA.
NOTES: Cleveland is one of several teams interested in center Greg Oden, the former No. 1 overall pick who hasn't played since 2009 because of knee injuries. The Akron Beacon Journal reported Friday the Cavaliers are expected to offer him a two-year contract with a team option for a third year after the Feb. 21 trade deadline. Oden, a former Ohio State star, has undergone three microfracture knee surgeries—two on his left knee. ... Of his participation in the 3-point shooting contest at All-Star weekend, Irving said, "Hopefully, I don't come in last place like the Skills Competition last year." ... Redick worked out before the game, but was held out again and is listed day to day. ... C Glen Davis (broken left foot), and F Al Harrington (right knee surgery) continue to be sidelined for Orlando.