In September 1918, Liston was hired by Wesleyan University as coach of the school's football team. He left Wesleyan in June 1919 to play professional baseball for the Wichita, Kansas team in the Western League. After spending the summer playing baseball in Wichita, Liston returned to Wesleyan as the head football coach in the fall of 1919. In two years as Wesleyan's football coach, Liston compiled a 10-3-0 record. His .769 winning percentage at Wesleyan remains the highest of any Wesleyan football coach with at least ten games as coach. Liston also coached the basketball and baseball teams at Wesleyan. In April 1920, Liston announced his resignation from Wesleyan.
After resigning from Wesleyan, Liston announced he was through with the coaching profession and that it was his intention to move to Kansas to work on the farm of his father-in-law.
He returned to coaching in 1930 with Baker University in Baldwin City, Kansas. He coached both football and basketball at Baker. He was the coach of the basketball team from 1930 to 1945 and led the school to Kansas Conference championships in 1930 and 1937. He also coached Baker's football teams and was for many years the school's winningest football coach with 97 wins; the career wins record was broken in 1992 by Charlie Richard.
Liston was also the founder of the National Association of Intercollegiate Athletics, organized the NAIA college basketball tournament, and a close friend of James Naismith. In 1945, Liston resigned his coaching position at Baker University to become the NAIB's first executive director; he held that position until his death in 1949. He was inducted into the Naismith Memorial Basketball Hall of Fame in 1975. Liston's biography at the Basketball Hall of Fame states: "With sheer initiative, drive, and foresight, Emil Liston fought for uniformity and equality in college athletics. A dedicated administrator, Liston envisioned a small college, national tournament and organized the NAIB (now known as the NAIA). The first NAIA tournament was played in Kansas City with an eight-team field in 1937."