The victory means the unbeaten Sooners probably will play top-ranked, unnbeaten Southern Cal in the Orange Bowl for the national crown.
Jason White was 22-of-29 for 254 yards and three scores for the Sooners (12-0).
Oklahoma scored touchdowns on its first three possessions, while its defense dominated the Buffaloes (7-5) the entire game.
Peterson scored on runs of one, three and 32 yards, while White had two 22-yard touchdown passes to Mark Clayton and added a five-yarder to Will Peoples.
"This is special," said Oklahoma Coach Bob Stoops. "We're not done yet. I'm proud of this team. they came out ready to play. They had an edge to them all week."