Ray Ray McCloud ran for 101 of his 158 yards and scored twice during the first quarter to lead host Sickles' thrashing.
But he sustained a right knee injury late in the first half and did not return. Sickles coach Brian Turner said McCloud would be evaluated but he did not expect the injury to be serious.
The win kept Sickles perfect at 3-0 in Class 7A, District 7 and moved it to 6-1 overall.
With their star on the bench, quarterback Isaac Holder and the Gryphons defense did the rest of the work. The offense scored on its first five drives. Holder was 10-of-16 for 76 yards and one touchdown. He also ran for 52 yards and a touchdown.
The defense was dominant, recovering three fumbles and limiting Gaither (3-4, 2-1) to 82 yards passing while sacking Alex McGough four times.
Daniel Lezotte added two field goals for Sickles, including a season-long 50-yarder.
"We were a little hungry. We feel like we let one slip away at Plant last week," Turner said of the 24-20 loss. "We came out fast on offense, and the defense was just stellar. "I wouldn't want to go against (our defense)."