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He was one of the artists who recorded at the Bristol Sessions in 1927, alongside more famous names such as Jimmie Rodgers and The Carter Family. He played the fiddle along with his son Arville, who played the guitar.

Reed was born completely blind. He was raised in a very conservative family, and acquired a violin at a young age. This is about all the information we can gather from him in his early life, as most of his events during this time were not written down nor talked about much in his later years.

While playing during a convention in 1927, Ralph Peer, who was the director of Bristol Sessions, heard Reed playing "The Wreck of the Virginian", and asked him if he wanted to make some recordings. Reed consented, and he recorded four songs with Arville's guitar accompaniment: "You Must Unload", "I Mean to Live for Jesus", "The Wreck of the Virginian", and "Walking in the Way with Jesus".

After the Bristol Sessions, Reed kept recording until 1929, which was the year of his most famous song's release "How Can a Poor Man Stand Such Times and Live?". After 1929, he stopped recording and lived out the rest of his life mostly in Sumner County, Tennessee and Mercer County, West Virginia. In 1956, Reed died, supposedly of starvation. He is buried in Elgood, West Virginia.

Reed's music was of a very conservative type; for example "Why Do You Bob Your Hair Girls?", in which he raged against women's hair style fashion of the 1920s. More than half of the songs he recorded were religious, spoke out against society's ills, and become known for their social commentary, which was somewhat uncommon then. This is a big reason why many people today consider him an early protest singer.

In 2007, Blind Alfred Reed was inducted into the West Virginia Music Hall of Fame, alongside other famous musicians from West Virginia. Also in 2007, a tribute album to Blind Alfred, named for one of his songs, was released. Always Lift Him Up: A Tribute to Blind Alfred Reed features nineteen of Reed's most famous songs, recorded by artists from West Virginia, such as Little Jimmy Dickens and Tim O'Brien.