He served as the head football coach the University of Utah, (1900–1903), the University of Southern California (1904–1907), and the Academy of Idaho—now known as Idaho State University—(1909–1914), compiling a career college football record of 60–24–4.

"[2] In 1904 Holmes became the first salaried head coach of the USC football team, and he compiled a 19–5–3 (.759) record over four seasons.

On November 4, playing a game at Stanford, the Methodists were trampled 16–0 by the traditional West Coast powerhouse; it was also USC's first game ever against major college competition, an experiment which the team would not repeat until 1914.

Given its schedule featuring small colleges, high schools, and military and club teams, USC in that period had little need for a football coach with Holmes' credentials, and he departed in 1908; the university eventually switched to rugby from 1911 to 1913.

He was succeeded as football coach by USC Law School graduate Bill Traeger.