Aaron Thibeaux Walker was born in Linden, Texas, of African American and Cherokee descent. His parents, Rance Walker and Movelia Jimerson were both musicians.

Early in the 1920s, the teenage Walker learned his craft amongst the street-strolling string bands of Dallas. His mother and stepfather, Marco Washington (member of the Dallas String Band) were musicians, and family friend Blind Lemon Jefferson sometimes joined the family for dinner. Walker was Jefferson's protégé and would guide him around town for his gigs. In 1929, Walker made his recording debut with a single for Columbia, "Wichita Falls Blues" / "Trinity River Blues," billed as Oak Cliff T-Bone. Oak Cliff was the community he lived in at the time and T-Bone a corruption of his middle name. Pianist Douglas Fernell was his musical partner for the disc. Walker married Vida Lee in 1935 and had three children with her. By the age of 26 he was working the clubs in Los Angeles' Central Avenue; sometimes as the featured singer and guitarist with Les Hite's orchestra.

His distinctive sound developed in 1942 when Walker recorded "Mean Old World" for Capitol Records. Much of his output was recorded from 1946 – 1948 on Black & White Records, including his most famous song, 1947's "Call It Stormy Monday (But Tuesday Is Just as Bad)". Other notable songs he recorded during this period were "Bobby Sox Blues" (a #3 R&B hit in 1946), and "West Side Baby" (#8 on the R&B singles charts in 1948).

Throughout his career Walker worked with top notch musicians, including Teddy Buckner (trumpet), Lloyd Glenn (piano), Billy Hadnott (bass), and Jack McVea (tenor sax).

Following his work with Black & White, he recorded from 1950 - 54 for Imperial Records (backed by Dave Bartholomew). Walker's only record in the next five years was T-Bone Blues, recorded over three widely separated sessions in 1955, 1956 and 1959, and finally released by Atlantic Records in 1960.

By the early 1960s, Walker's career had slowed down, in spite of a hyped appearance at the American Folk Blues Festival in 1962 with Memphis Slim and Willie Dixon, among others. Several critically acclaimed albums followed, such as I Want a Little Girl. Walker recorded in his last years, from 1968 - 1975, for Robin Hemingway's Jitney Jane Songs music publishing company, and he won a Grammy Award in 1971 for Good Feelin' (Polydor), produced by Hemingway. Fly Walker Airlines (Polydor) also produced by Hemingway, was released in 1973.

Persistent stomach woes and a 1974 stroke slowed Walker's career down to a crawl. He died of bronchial pneumonia following another stroke in March 1975, at the age of 64. Walker was interred in the Inglewood Park Cemetery in Inglewood, California.

Walker was posthumously inducted into the Blues Hall of Fame in 1980, and into the Rock and Roll Hall of Fame in 1987.
Chuck Berry named Walker and Louis Jordan as his main influences. B.B. King cites hearing Walker's "Stormy Monday" record as his inspiration for getting an electric guitar. Walker was also the childhood hero of Jimi Hendrix, and Hendrix imitated some of Walker's ways throughout his life. Years before Hendrix, Walker was playing guitar with his teeth or in strange positions. "Stormy Monday" was a favorite live number for The Allman Brothers Band.