The Red Devils improved to 9-4 overall and 2-2 in the conference. The victory was their fifth in a row after a 4-4 start.
Holton built an big 40-12 lead by halftime, then cruised in the second half.
Kaylie Piper paced the Red Devils with 15 points, Shelbey Younts added 13, Courtney Slater had 12 and Dani Tanner scored 10.
Ami Tateyama led Hesperia with 14 points while Allison Bayle added eight.