Irving was sidelined with flu-like symptoms, and Horford got the evening off to rest. Horford missed seven games in December with left knee soreness.
Terry Rozier took Irving's spot in the starting lineup and led the Celtics with 26 points, eight rebounds and six assists.
Aron Baynes started in place of Horford and had two points and eight rebounds.
Boston has now won five straight, while the Cavaliers have lost 17 of their past 18 and have the NBA's worst record at 9-40.