Quarterback Reggie Collier and tailback Ricky Floyd each produced three touchdowns to power the 14th-ranked Golden Eagles over the 20th-ranked Seminoles in Tallahassee, Fla.
Collier, who completed seven of eight passes, threw for two touchdowns and ran 69 yards for another score. He rushed for more than 100 yards and continued his streak of not having thrown an interception this season.
Floyd scored on a pass and a 12-yard run, and returned a punt 73 yards late in the final period for his third touchdown.
The undefeated Golden Eagles (8-0-1) scored the first seven times they had the ball.
The Southern Mississippi defense, ranked No. 1 nationally both in pass and scoring defense, stymied the Seminoles, who crossed midfield only once in the first half and then immediately were pushed back into their own territory.
It was the worst loss in five years for the Seminoles. They had five turnovers, each of which resulted in a Southern Mississippi score.
"They just came out and really kicked us around," said Florida State Coach Bobby Bowden. "I'm embarrassed. I was embarrassed at the end of the first quarter," when the score was only 14-0.
Southern Mississippi led 30-0 at halftime, and Florida State didn't score until late in the third period, when substitute quarterback Blair Williams completed a 50-yard pass to wide receiver Dennis McKinnon.