A prominent figure in Appalachian folk music,[2] Holcomb was the inspiration for the term "high, lonesome sound", coined by folklorist and friend John Cohen.

In addition to playing the banjo and guitar, he was a competent harmonica and fiddle player, and sang many of his most memorable songs a cappella.

[4] A coal miner, construction laborer and farmer for much of his life,[5] Holcomb was not recorded until 1958, after which his career as a professional musician was bolstered by the folk revival in the 1960s.

Due to what he described as injuries he sustained during his long career as a laborer, Holcomb was eventually unable to work for more than short periods, and his later income came primarily from his music.

Suffering from asthma and emphysema as a result of working in coal mines, he died in a nursing home in 1981, at the age of 68.