The Bulls outscored the Cavaliers by 21 points during the second and third periods while picking up their fifth straight win. Chicago improved its road record to 20-6 and advanced its record within the Central Division to 7-1.
Derrick Rose had 19 points and nine assists and Carlos Boozer contributed 13 points and 11 rebounds for the Bulls.
Chicago shot 52 percent from the field and connected on half its 20 3-point shots.
Antawn Jamison scored 22 points to lead Cleveland, which has lost four straight.