Andrew Nicholson contributed 13 and Nikola Vucevic had 12 points and 19 rebounds for the Magic (16-41), who hadn't won on the road since Jan. 12 against the Los Angeles Clippers.
E'Twaun Moore had 12 points and a career-high 10 assists, while Maurice Harkless had 10 points for the Magic.
The Magic won for just the seventh time all season on the road while also snapping a five-game skid overall.
The Sixers lost their sixth straight game, their longest streak in nearly three years.
Damien Wilkins led the struggling Sixers with a season-high 14 points, while Jeremy Pargo added 14. Dorell Wright also had 11 and Evan Turner 10 for Philadelphia, which fell a season-worst 11 games under .500 at 22-33.
This latest defeat came against the Magic, who started two rookies and featured five rookies and three second-year players on their roster.
Orlando also entered this game having lost 28 of its last 31.
The Magic opened the third quarter on an 11-0 run and then began the fourth on a 17-3 spurt to go ahead 85-64.
Harkless and Vucevic, who were acquired in the blockbuster four-team, 12-player Dwight Howard trade in the offseason, keyed the two runs for the Magic.
The Sixers received center Andrew Bynum in that trade, but the two-time All-Star has yet to play because of bilateral knee bone bruises.
Orlando is also dealing with its share of injuries, but it was hardly evident on this night. It played without guard Jameer Nelson (left knee) and forwards Glen Davis (fractured left foot) and Hedo Turkoglu (NBA suspension).
The Magic shot 51 percent in the first half, led by as many as seven points, and took a 47-42 advantage into the locker room.
NOTES: Magic F Al Harrington made his debut this season and scored nine points. Harrington had been dealing with sore knees. . The Magic have unveiled 19 different starting lineups, tied for the most in the league. . Sixers F Thaddeus Young reached double figures in rebounding for the second straight game since returning from a strained left hamstring. . Sixers G Jrue Holiday had 10 assists.