The Red Devils led 40-37 at the end of the third quarter, but took control with a 19-9 run in the fourth.
Holton improved to 6-5 overall and 2-3 in the conference. Hesperia fell to 1-6 and 1-4.
Kyle Wildfong led Holton with 22 points while Kevin Slowik added 18.
Hesperia was paced by Scotty Peters with 20 points.