Big Maybelle was born Mabel Louise Smith on May 1, 1924 in Jackson, Tennessee. She played piano and sang in gospel choir as a child, but as a teen she embraced rhythm and blues. She took first prize at a Memphis talent show in 1932, and soon after her professional career began, including stints with Dave Clark's Memphis Band and the all-female International Sweethearts of Rhythm.
In the 1940s she joined Christine Chatman's Orchestra on piano, and in 1944 had her first recording sessions with Chatman. She recorded as a solo artist for the first time in 1947 under the name Mabel Smith for King Records, backed by Oran "Hot Lips" Page. She also sang with Tiny Bradshaw's band from 1947 to 1950.
The decade of the 1950s was the peak of her career. In 1952, producer Fred Mendelsohn signed her to Okeh Records and coined her stage name of "Big Maybelle". Her first Okeh recording, "Gabbin' Blues", hit #3 on the Billboard R&B chart, and the hits "Way Back Home" and "My Country Man" followed in 1953. Her version of "Whole Lotta Shakin' Goin' On" was produced by Quincy Jones in 1955, two years before Jerry Lee Lewis recorded it. Another hit, "Candy", came in 1956 for Savoy Records, and was followed by appearances at the Apollo Theatre in New York City and at the 1958 Newport Jazz Festival, which was part of the movie Jazz on a Hot Summer Day (1960).
Big Maybelle continued to record into the 1960s, but her popularity and health both declined. Her last hit was in 1967 with her version of "96 Tears", made famous by the rock band ? and the Mysterians. She moved to Cleveland in 1971 to live with relatives,and died here in 1972. At the time of her death, local DJ Bill Randle (of WERE) described her as "a highly respected blues singer in the Bessie Smith, Big Mama Wakefield tradition." Her last album, The Last of Big Maybelle, was released posthumously in 1973.