The singer came from humble beginnings. Her mother picked cotton to support Houston and her three sisters. During her youth, the family relocated to Long Beach, CA. As an adult, Houston graduated from high school, got married, had two children, and was later divorced. She got a job in the health care field. Staying active in music, she became a member of the Art Reynolds Singers, singing lead on their popular single cover of "Glory Glory Hallelujah" on Capitol. 5th Dimension manager Marc Gordon was impressed by her vocal skills and helped to get her a recording deal with Dunhill Records. In 1969, renowned songwriter Jimmy Webb produced her debut LP, Wildflower. One single, a cover of Laura Nyro's "Save the Country," charted in early 1970.

During 1971, Houston signed with Motown, with her label debut, Thelma Houston, being issued on the MoWest imprint. Over the next few years, the singer issued numerous singles that failed to be hits, though one Motown single, the catchy "You've Been Doing Wrong for So Long," lingered in the lower half of the R&B charts. She can be seen in the classic Billy Dee Williams/James Earl Jones Negro League baseball movie The Bingo Long Traveling All Stars and Motor Kings, produced by Motown and released through Universal Pictures. Houston's background vocals are woven throughout Jermaine Jackson's 1976 gold LP My Name Is Jermaine.

Finally, synchronicity in Houston's favor came in a big way in the form of the release of the 1976 LP Any Way You Like It, produced by Hal Davis (Diana Ross' "Love Hangover") and issued on Motown's Tamla imprint. Davis had heard the Blue Notes' version at a party while he was in the process of recording tracks for the album. First taking off in disco and on both disco-oriented and soul music radio stations, "Don't Leave This Way" went to number one R&B in February 1977 and number one pop in April 1977 (Billboard). It can be found on Rhino's Disco Box, Billboard Top Hits: 1975-1979, Disco Nights, Vol. 9: Motown Dance, 70s Disco Ball Party Pack, and The Disco Years, Vol. 1: Turn the Beat Around. A 12" version is on Pure Disco and Essential 12'': The 70s.

Her other hits include "If It's the Last Thing I Do," "I'm Here Again," "Saturday Night, Sunday Morning," and the RCA single "If You Feel It." A pre-mega stardom Jimmy Jam and Terry Lewis produced the smooth, percolating Top 20 R&B dance track "You Used to Hold Me So Tight" from her 1984 MCA album Qualifying Heat. She duets with the Winans on a cover of Bill Withers' "Lean on Me," the title track of the same-named 1989 Morgan Freeman movie. She does backing vocals on guitarist Scott Henderson's 1997 Atlantic CD Tore Down House.

Houston appeared on cable channel VH1's 100 Greatest Dance Songs during October 2000. Her first new album in 17 years, A Woman's Touch, appeared in 2007 from Shout Factory.