Andrew David Holt Jr. was born to Andrew David and Mary Elizabeth Brown Holt on December 4, 1904 in Milan, Tennessee. He completed his undergraduate work at Emory University, after which he began working in primary and secondary education. In 1937, he completed his PhD degree at Columbia University's Teacher's College and began working as Executive Secretary for the Tennessee Education Association (TEA). He held this position until 1950, interrupted only by two years spent serving in World War II. While working for the TEA, Holt became dedicated to the cause of improving Tennessee's public education system and proved instrumental in instituting a retirement system for teachers and a statewide sales tax to support education.

In 1950, Holt came to the University of Tennessee to serve as Executive Assistant to President Brehm. In 1953, he was promoted to Vice-President, and was finally made President in 1959. He remained in this position until 1970. Holt proved to be one of the University's most enthusiastic and productive presidents: during his tenure, enrollment tripled, faculty and staff doubled, state appropriations rose over 400%, and numerous new institutions and institutional relationships were established. Holt was also extremely popular: known as a kind, modest, and religious man, he proved to be an extremely effective goodwill ambassador for and consensus builder within the University. As one administrator put it, Andy could get people to work themselves to death for him. He was forever telling everybody how good they were. Holt died in Knoxville on August 7, 1987.