Born Irma Lee, as a teenager she sang with a Baptist church choir. She auditioned for Specialty Records at the age of 13. By the time she was 19, she had been married twice and had four children. Keeping her second ex-husband’s surname, she worked as a waitress in New Orleans, occasionally singing with bandleader Tommy Ridgley, who helped her land a record deal with the local Ron label. Her first single, “Don’t Mess with My Man,” was released in late 1959, and reached number 22 on the US Billboard R&B chart.
She then began recording on the Minit label, working with songwriter and producer Allen Toussaint on songs including “It’s Raining” and “Ruler of My Heart”, which was later reinterpreted by Otis Redding as “Pain in My Heart”. Imperial Records acquired Minit in 1963, and a string of successful releases followed. These included “Wish Someone Would Care”, her biggest national hit, its B-side “Breakaway”, written by Jackie DeShannon and Sharon Sheely, “Anyone Who Knows What Love Is (Will Understand)”, co-written by a young Randy Newman and future country star Jeannie Seely, and its B-side, “Time Is on My Side”, a song previously recorded by Kai Winding and later by the Rolling Stones.
Her first four Imperial singles all charted on Billboard’s pop chart, but her later releases were less successful. Unlike her contemporaries Aretha Franklin, Gladys Knight and Dionne Warwick, she never managed to cross over into mainstream commercial success. She recorded for Chess Records in 1967–68 with some success; her version of the Otis Redding song “Good to Me” reached the R&B chart. She then relocated to California, releasing records on various small labels, before returning to Louisiana, and in the early 1980s opened the Lion’s Den Club. Thomas and her husband still own the Lion’s Den Club near the French Quarter of New Orleans.
Down By Law, the 1986 independent film by Jim Jarmusch featured “It’s Raining” in the soundtrack. The film’s actors Roberto Benigni and Nicoletta Braschi, whose characters fell in love in the movie, danced to the song.
After several years’ break from recording, she was signed by Rounder Records, and in 1991 earned her first Grammy Award nomination for Live! Simply the Best, recorded in San Francisco. She subsequently released a number of traditional gospel albums, together with more secular recordings. The album Sing It! (1998) was nominated for a Grammy in 1999.
Thomas is still active as a performer, appearing annually at the New Orleans Jazz & Heritage Festival. She reigned as Queen of the Krewe du Vieux for the 1998 New Orleans Mardi Gras season. She often headlined at her own club, but it went out of business due to Hurricane Katrina, which caused her to relocate to Gonzales, Louisiana, 60 miles (97 km) from New Orleans. According to her website she is now back in her home in New Orleans.
In April 2007, Thomas was honored for her contributions to Louisiana music with induction into the Louisiana Music Hall of Fame. Also in 2007, Thomas accepted an invitation to participate in Goin’ Home: A Tribute to Fats Domino where, singing with Marcia Ball, she contributed “I Just Can’t Get New Orleans Off My Mind”. The same year she won the Grammy Award for Best Contemporary Blues Album for After the Rain.
In August 2009, a compilation album with three new songs titled The Soul Queen of New Orleans: 50th Anniversary Celebration was released from Rounder Records to commemorate Thomas’ 50th year as a recording artist.
Thomas was the subject of the 2008 New Orleans Jazz & Heritage Festival poster. She was chosen as the subject before the painting was chosen for the poster. Artist Douglas Bourgeois painted the singer in 2006. In 2010, Thomas rode in the New Orleans parade “Grela”. In April that year, Thomas performed at the Corner Hotel, Richmond, Victoria, Australia.
In 2011, Thomas performed twice at the Bluesfest music festival in Byron Bay, New South Wales, Australia. On April 24, she performed on the Crossroads stage, coming on after Mavis Staples; then on April 25, she headlined the Crossroads stage, coming on after Jethro Tull and Osibisa.
In 2013, Thomas was nominated for a Blues Music Award in the “Soul Blues Female Artist” category, which she duly won. She won the same award in 2014.