David Piland was 15 of 23 for 148 yards and a touchdown and John O'Korn threw for 107 yards and three touchdowns in a backup role. Kenneth Farrow added 97 yards on the ground for the Cougars, which piled up 627 yards of offense - 372 on the ground - in their first game in the American Athletic Conference.
Daniel Spencer caught nine passes for 102 yards and two touchdowns and ran for a third score for Houston, which was penalized 14 times for 126 yards.
Southern's Dray Joseph finished 27 of 36 for 268 yards and two touchdowns. Samuel Altman caught four passes for 74 yards and a score and Willie Quinn had six catches for 77 yards and a touchdown.
