Speckled Red was born in Hampton, Georgia. He was the older brother of Piano Red. Their nicknames were derived from both men being albinos. The brothers were separated by almost a generation and never recorded together. Speckled Red and Piano Red both played in a raucous goodtime barrelhouse boogie-woogie style, although Speckled Red played slow blues more often. Both recorded versions of "The Right String (But the Wrong Yo-Yo)", Speckled Red in 1930 and Piano Red, who had a hit with the song 20 years later.

Prior to his birth the family had moved for brief periods to Detroit, Michigan, and then Atlanta, Georgia, after his father violated Jim Crow laws, before settling in Hampton, Georgia. The family, consisting of Perryman and seven brothers and sisters, had little musical background. Speckled Red was a self-taught piano player, influenced primarily by his idol Fishtail and by Charlie Spand, James Hemingway and William Ezell and initially inspired by Paul Seminole in a movie theatre. He also learned to play the organ at his church

Charlie O'Brien, a St. Louis policeman and something of a blues aficionado who applied many of his professional investigative methods to track down old bluesmen during the 1950s, "rediscovered" Speckled Red on December 14, 1954, who subsequently was signed to Delmark Records as the label's first blues artist. He experienced a small revival of interest in his music during the late 1950s and 1960s, his abilities still considerable, and worked around the St. Louis-area jazz scene, regularly as the intermission pianist for the Dixie Stompers, performing concerts with Dixie Mantinee and the St. Louis Jazz Club, played the Goldenrod Showboat, and played the University of Chicago Folk Festival in 1961, went to Dayton, Ohio, with Gene Mayl's Dixieland Rhythm Kings, and toured Europe in 1959 with Chris Barber. Several recordings were made in 1956 and 1957 for the Tone, Delmark, Folkways, and Storyville record labels.

His age, however, had become a factor, and the remainder of the 1960s saw scattered performances. He died of cancer on January 2, 1973, in St. Louis, at the age of 80.