Edwards was a friend to the legendary musician Robert Johnson and was present on the fateful night Johnson drank the poisoned whiskey that took his life. Folklorist Alan Lomax recorded Edwards in Clarksdale, Mississippi in 1942 for the Library of Congress. Edwards recorded a total of fifteen sides of music. The songs included "Wind Howlin' Blues" and "The Army Blues." He did not record again commercially until 1951, when he recorded "Who May Your Regular Be" for Arc Records under the name of Mr Honey
Edwards is still touring the country performing and is the author of one book, The World Don't Owe Me Nothin', published in 1997 by Chicago Review Press. The book recounts his life from childhood, his journeys through the South and his arrival in Chicago in the early 1950s. A companion CD by the same title was released by Earwig Records shortly afterwards. He has also recorded at a church-turned-studio in Salina, Kansas and released albums on the APO record label.
Honeyboy has written several blues hits, including "Long Tall Woman Blues" and "Just Like Jesse James". His discography for the 1950s and 1960s amounts to nine songs from seven sessions.
Edwards is one of, if not the last, original delta blues guitarists still performing. In October 2004, the last four original delta blues musicians gathered together in Dallas, Texas for a once-in-a-lifetime concert. The line-up consisted of: Honeyboy Edwards, Pinetop Perkins, Henry Townsend, and Robert Lockwood, Jr. But two years later in 2006, Townsend died aged 96, and Lockwood also died aged 91. Pinetop Perkins still continues to tour, mainly in the USA.
He appeared as himself in the 2007 film, Walk Hard: The Dewey Cox Story. Edwards still continues to perform across the world, performing up to 100 concerts a year. Edwards announced that he will be retiring from international touring this year, and his UK tour that took place in May and June 2008 was the last time he would perform in the UK.
His albums White Windows, The World Don't Owe Me Nothing, Mississippi Delta Blues Man, and a recent album in which he appears with Robert Lockwood, Jr., Henry Townsend and Pinetop Perkins, Last Of The Great Mississippi Delta Bluesmen: Live In Dallas, were all nominated for the W. C. Handy Award. The latter album was also nominated for a Grammy Award in 2008, and later won the award.