In 1984, Byars finished second in the Heisman Trophy voting (behind Doug Flutie) after a season where he gained an OSU record 2,441 all-purpose yards, including a then-school record 1,764 rushing yards and 22 touchdowns. That season featured a game against Illinois (Ohio State won this game 45-38 on October 13, 1984) in which Byars led a comeback from a 24-0 deficit, rushing for 274 yards and five touchdowns, the last with 36 seconds remaining in the game. On his fourth touchdown run, going for 67 yards, he famously lost his left shoe at the Illini 40 but never broke stride. Byars was a unanimous first-team All-America selection, and voted the Big Ten ConferenceMost Valuable Player. His running backs coach that year was a young Jim Tressel, who would later become the Buckeyes' head coach.
Byars was a preseason favorite for the 1985 Heisman, but fractured the bone in his right foot near the little toe in preseason practice. He missed the first five games of the 1985 season, and returned too early. He reinjured the broken bone in his second game back and missed the remainder of the regular season. He attempted to return for the Citrus Bowl game on December 28, but reinjured his foot again in the second Ohio State offensive series of the game. Many observers note that throughout the remainder of his football career Byars was never as dominant a player as he had been in 1984.
Despite losing almost his entire senior year, Byars finished his college career at Ohio State with 4,369 total yards, 3,200 rushing yards, and 50 touchdowns. His 50 touchdowns remain the second most in school history.
A superb rusher, blocker, and pass receiver, Byars was a vital contributor for every team he played on. In 1988 he rushed for 517 yards, recorded 71 receptions (ranking him 9th in the NFL), and scored 10 touchdowns. In the Eagles 20-12 loss to the Chicago Bears in the postseason, he rushed for 34 yards and caught 9 passes for 103 yards. In 1990, he recorded 81 receptions for 819 yards, the third most receptions in the NFL, rushed for 141 yards, and even completed 4 of 4 passes for 53 yards and 4 touchdowns. In the 1996 season, Byars made his first and only championship appearance, playing with the Patriots in Super Bowl XXXI. His team lost the game 35-21, but the 33-year old Byars had a good performance in it, catching 4 passes for 42 yards and a touchdown. As a member of the New York Jets in 1998, Byars is unfortunately best remembered for fumbling during the AFC Championship Game against the Denver Broncos (which the Jets were winning at the time, 10-0), which led to the Broncos scoring 23 unanswered points and winning the game. 
In his 13 seasons, Byars rushed for 3,109 yards, caught 610 passes for 5,661 yards, returned five kickoffs for 94 yards, and completed 6 of 13 passes for 119 yards and six touchdowns, with one interception. He also scored 54 touchdowns (23 rushing and 31 receiving). His six passing touchdowns are the third highest total by a running back in NFL history.