Holcomb was named Miami University's head football coach for the 1942 season succeeding Frank Wilton. His first team went 3–6 which equaled the number of wins of the three previous years for the Redskins. The next year Holcomb and the Redskins posted a winning record of 7–2–1. This team was dominated by defense, only allowing their opponents to score in double digits twice; A 34–12 win over Bradley University and a 35–0 blow out loss to Arkansas A&M. In his two years as Miami’s head coach he compiled an overall record of 10–9–1. He left Miami to become an assistant coach for Earl Blaik at the United States Military Academy. He was replaced as Redskins coach by future Pro and College Football Hall of Fame coach Sid Gillman who was one of Holcomb's top assistant coaches.
While an assistant football coach for the United States Military Academy, Holcomb was head coach of the men’s basketball team for two seasons from 1945 through 1947. He led the cadets to two straight winning seasons of 9–6 and 9–7.
During Holcomb’s tenure as Boilermakers head coach he compiled a record of 35–42–4. His best year was 1952 when he led the Boilermakers to a Big Ten Conference co-championship and a #18 ranking in the final poll. Despite having only a 4–3–1 overall record, Holcomb's team played well in conference with a 4–1–1 record. Holcomb’s Purdue teams are, perhaps, best remembered for ending Notre Dame's 39-game unbeaten streak when his Boilermakers defeated the Irish, 28–14, in the second game of the 1950 season. Holcomb was known for developing solid quarterbacks including Bob DeMoss, Dale Samuels and Len Dawson. These players helped grow a strong tradition at Purdue of great quarterback play. On December 12, 1955, After his nine seasons at Purdue, Holcomb left Purdue to accept the athletic director position at the Northwestern University
He was promoted to replace Ed Short as general manager in September 1970, the last month of a season in which the White Sox finished with its worst record in team history at 56–106. He began overhauling the ballclub by firing managerDon Gutteridge and replacing him with Chuck Tanner (third-base coach Bill Adair served as the interim for ten games during the transition).