As a sophomore, Sisemore was a regular on the 1970 Longhorn team that built an unbeaten streak to 31 games. The next year Sisemore blossomed into one of the nation's best linemen as he had the first of two consecutive seasons (1971 and 1972) where he was both an all-conference and Unanimous All-America selection. In his 1972 senior year, Texas won its third consecutive Southwest Conference title and gained its third straight Cotton Bowl Classic bid. He was inducted to the College Football Hall of Fame in 2002.
Sisemore was an impact player with the Philadelphia Eagles, especially after the arrival of legendary coach Dick Vermeil in 1976. The Eagles gradually improved under Vermeil, and reached the NFL playoffs in 1978 and 1979, and Super Bowl XV in 1980. Sisemore was a big part of an offense that featured Philadelphia sports legends such as quarterback Ron Jaworski and running back Wilbert Montgomery. Sisemore is considered one of the greatest offensive linemen in franchise history.