At the University of Notre Dame, Lisch was part of Dan Devine's first recruiting class in 1975. He made his first start in place of injured Rick Slager in 1976, achieving a 40-27 victory against Miami. He started the first three games of 1977 but then would yield the starting job to Joe Montana. Lisch would finally be named the permanent starting quarterback as a fifth-year senior in 1979, winning seven of ten starts, highlighted by his 336-yard passing effort as the Irish rallied from a 17-3 deficit against South Carolina for an 18-17 victory.
Lisch's rather bad NFL career caused him to receive the "honor" as the worst player in NFL history from sports blog Deadspin in 2011, saying:
"Sure, Leaf and Russell were bigger busts. Lisch, after all, was a fourth-round pick who had backed up Joe Montana at Notre Dame. But if you have one game you need to lose, and you require a quarterback to take you there, Lisch is — hands down — the man you want. In 115 career attempts he threw one touchdown and 11 interceptions. That one touchdown came in St. Louis on Oct. 9, 1983. The pass traveled a single yard, to tight end Doug Marsh. With Neil O'Donoghue's extra point, the Redskins' lead was cut to 31-14 — late in the contest.