Homesick James was born in Somerville, Tennessee, United States, the son of Cordellia Henderson and Plez Williamson Rivers, who were both musicians.

In 1932, he relocated to Chicago, Illinois,[9] working with Horace Henderson's band at the Circle Inn and with the pianist Jimmy Walker at the Square Deal Club.

[11] He was a member of Elmore James's band from 1955 to 1963, contributing to such tracks as "Dust My Broom," "The Sky Is Crying," and "Roll and Tumble.

[12][13] As a solo performer, he recorded for the Colt and USA labels in 1962, including a cover version of Robert Johnson's "Crossroads".

[17] From 1972 through 2006, Homesick lived in Chicago, Nashville, Atlanta, Fresno and finally Springfield, Missouri, where he died at the age of 96.