Sanders played for the Oklahoma State Cowboys from 1986 to 1988, and wore the number 21. During his first two years, he backed up All-American Thurman Thomas. In 1987 he led the nation in kickoff return yards. Thomas moved on to the NFL, and Sanders became the starter for his junior year.
In 1988, in what has been called the greatest season in college football history, Sanders led the nation by averaging 7.6 yards per carry and over 200 yards per game, including rushing for over 300 yards in four games. Despite his massive workload of 344 carries, Sanders was still used as the team's punt and kickoff returner, adding another 516 yards on special teams. He set college football season records with 2,628 yards rushing, 3,248 total yards, 234 points, 39 touchdowns, of which 37 were rushing (also a record), 5 consecutive 200 yard games, scored at least 2 touchdowns in 11 consecutive games, and 9 times he scored at least 3 touchdowns. Sanders also ran for 222 yards and scored 5 touchdowns in his three quarters of action in the Holiday Bowl - a game that was not included with his season statistics. Sanders won the Heisman Trophy as the season's most outstanding player. Barry is the only Heisman winner to be notified of his achievement in Tokyo, Japan, where he and his Cowboy teammates were awaiting the final game of the season. He then chose to leave Oklahoma State before his senior season to enter the NFL draft.
Barry Sanders became Oklahoma State's first Heisman winner and also became the first winner to be notified of his selection while in Japan while playing in a special NCAA game in Tokyo. He swept all six sections and ran away with the voting as he beat out the four quarterbacks who trailed him in the balloting.