Raised in Belzoni, Mississippi, Denise LaSalle sang in local churches before moving to Chicago in the early 1960s. She sat in with R&B musicians and wrote songs, influenced by country music as well as the blues, before winning a recording contract with Chess Records in 1967. Her first single, "A Love Reputation" was a modest regional hit.
After establishing an independent production company, Crajon, with her then husband Bill Jones, her first major success came in 1971 when her self-penned song, "Trapped By A Thing Called Love", released on Westbound Records, made #1 on the national R&B chart and #13 on the Billboard Hot 100 chart. The song ranked at #85 on the 1971 year end chart. The RIAA gold disc award was made on 30 November 1971 for a million sales. Follow-ups "Now Run And Tell That" and "Man Sized Job" also made the R&B Top Ten, and she continued to have hits on Westbound and then on ABC Records through the mid 1970s. She also carried on as a record producer and live performer. Her co-penned song "Married, But Not to Each Other" was included in the 1979, The Best of Barbara Mandrell, compilation album.
In 1980 she signed as a singer and songwriter with Malaco Records, for whom she released a string of critically acclaimed albums through the 1980s and 1990s, starting with Lady in the Street (1986) and Right Place, Right Time (1984). Both albums became major successes among soul blues, R&B and soul fans and on urban radio stations. In 1985 she enjoyed her only recognition in the UK Singles Chart, when her cover version of Rockin' Sidney's, "My Toot Toot", reached #6.
LaSalle appeared at the 1984 and 1993 versions of the Long Beach Blues Festival, and also in 1993 she performed at the San Francisco Blues Festival. Her 1997 album Smokin' In Bed was an unexpected commercial success.
She continues to work as a live performer, particularly at festivals, and more recently has issued more gospel-tinged material. 2011 she was inducted to the Blues Hall of Fame.