James G. Lyerly was born in Granite Quarry, North Carolina. He received his secondary education at Mt. Pleasant Collegiate Institute in Mount Pleasant, North Carolina. He graduated from Roanoke College in 1915 and received his M.D. degree from the Medical College of Virginia shortly thereafter.
He remained at the Medical College of Virginia for fourteen years as an assistant professor of neurological surgery and professor of oral surgery at the School of Dentistry at MCV. Lyerly resigned in 1934 to establish a practice in neurological surgery is Jacksonville.
Lyerly was a founding member of the Harvey Cushing Neurosurgical Association and was also a fellow of American College of Surgeons. He was the former chief of neurosurgery at St. Vincent's, St. Luke's, and Brewster hospitals. He was the past president of Duval County Medical Association, and is consultant neurosurgeon of the Veterans Administration hospital. He was an active Lutheran.
James G. Lyerly Sr. received the Roanoke College Medal in 1969.