Holmes is best known for being one of the first two black students to attend the University of Georgia, an experience he described as "hard, a time of isolation in which I learned tolerance." He completed his education at Georgia with membership in Phi Beta Kappa and cum laude honors at graduation.
Holmes also was the first black student at Emory's medical school, following the Georgia Supreme Court ruling allowing private institutions to admit non-white students. He had stated publicly his preference to attend medical school at Emory, and applied and was accepted in the spring of 1963.
In an intervew published in 1964 in an Episcopal diocesan newsletter, Holmes said that at Emory, he felt he was accepted by his teachers and fellow students as "just another person and another student and not especially as a Negro student. Things are better at Emory all the way around. There is less tension. More cordiality, friendship and companionship."
After an internship and military service, Holmes returned to Emory for his residency, then joined the fauclty as assistant professor in the Orthodpaedic Division of the Department of Surgery. He later became chief of orthopaedics at the Veterans Administration Hospital (now Medical Center), then went into private practice. In 1989, he was named medical director at Grady Hospital, a position he held until February, when he became chief of orthopaedic surgery at Grady. Charles Hatcher Jr., vice president for Health Affairs, nominated him as medical director at Grady, saying, "I've seen him in difficult situations, both medically and politically, and he knows how to assess what's happening and handle the situation well." Holmes also held an appointment as assistant professor at the medical school.