Born March 6, 1893, in Greenwood, Mississippi, Lewis acquired the nickname "Furry" from childhood playmates. At the age of seven he and his family moved to Memphis, where young Lewis took up the guitar under the tutelage of a man whose name he recalled as "Blind Joe." Blind Joe apparently was versed in nineteenth century song and taught his protégé "Casey Jones" and "John Henry," songs based around the exploits of heroic figures. Lewis would later record these two songs for the Victor and Vocalion labels respectively. By 1908, he was playing solo for parties, in taverns, and on the street. He also was invited to play several dates with W.C. Handy’s Orchestra.
Lewis hoboed around the country until 1917, when he lost a leg in a railroad accident. He returned to Memphis, playing in association with Jim Jackson, Gus Cannon (who would form Cannon's Jug Stompers for recording dates), and Will Shade.
Though primarily a solo performer, Lewis worked with this combination in a variety of clubs on Beale Street including the famous Pee Wee's (now the site of a Hard Rock Café) into the 1920s. The loss of a leg did not prevent him from touring during the early 1920s with the Dr. Willie Lewis Medicine Show, where he made the acquaintance of a young Memphis Minnie. His travels exposed him to a wide variety of performers including Bessie Smith, Blind Lemon Jefferson, and Texas Alexander. Like his contemporary Frank Stokes, he tired of the road and took a permanent job in 1922. His position as a street sweeper for the City of Memphis, a job he would hold until his retirement in 1966, allowed him to remain active in the Memphis music scene.
In 1927, Lewis cut his first records in Chicago for the Vocalion label. A year later he recorded for the Victor label at the Memphis Auditorium in a session that saw sides waxed by the Memphis Jug Band, Jim Jackson, Frank Stokes, and others. He again recorded for Vocalion in Memphis in 1929. The recordings from these dates exhibit a nimble, clean, and versatile picking style that provides an excellent counterpoint to his complex verses. Several of his recordings (notably "Judge Harsh Blues" and "Cannonball Blues") display Lewis's bottleneck slide playing, a style in which he was proficient but not a master. His vocal range was limited but he compensated by composing humorous verses that were by turns bawdy, sly, boasting, and pleading.