James scored 27 points to go with eight rebounds and seven assists for the Cavs, whose lead over the Boston Celtics for first place in the East is one game with three to play.
The two franchises play again Sunday in Atlanta.
The Hawks' regular starting five all sat out. Paul Millsap, Kent Bazemore, Dwight Howard and Dennis Schroder were held out for rest after a 123-116 win over Boston on Thursday. Thabo Sefolosha (right groin strain) has been out and Atlanta didn't want to play Millsap or Bazemore on consecutive nights after recent bout with injuries.
Coach Mike Budenholzer said before the game that Schroder (right mid-foot sprain) would play and start against the Cavs, but after his pregame remarks the Hawks announced that both Schroder and Howard were out, too.
The Hawks still had six players score in double figures. They also shot 50.6 percent from the field and led by as many as 20 points.
The Cavs' four-game winning streak was snapped in stunning fashion.
NOTES: Cavs C Tristan Thompson (sprained right thumb) missed his second consecutive game. Coach Tyronn Lue had no timetable for his return but said he wanted Thompson to play again before the regular season ends if possible. ... Lue said he will rest G Kyrie Irving and F LeBron James for the playoffs but not until the Cavs clinched the East. ... The last time these teams played on March 3 in Atlanta, the Cavs set an NBA record making 25 3-pointers (on 46 attempts). Cleveland was 2 of 14 from 3-point range in the first quarter on Friday.