The senior girls will battle the juniors and sophomores as the football players cheer on the sidelines.
Admission is $3 and all proceeds benefit Conway Special Olympics and Coats for Kids.
This year there will also be a powder puff "court," made up of fourth grade representatives from each elementary school, with a "king" crowned at half time.
The Powder Puff game is sponsored by the Conway High School Caring Cat Club. It begins Wednesday night at 7 pm.