Reynolds was born Mary Frances Reynolds in El Paso, Texas, the second child of Maxine N. (née Harmon; 1913–1999) and Raymond Francis Reynolds (1903–1986), who was a carpenter for the Southern Pacific Railroad. Reynolds was a Girl Scout and a troop leader (a scholarship in her name is offered to high-school age Girl Scouts). Her family moved to Burbank, California, in 1939, and she was raised in a strict Nazarene faith. At age 16, while a student at Burbank's John Burroughs High School, Reynolds won the Miss Burbank Beauty Contest, a contract with Warner Brothers, and acquired her new first name.

Debbie Reynolds regularly appeared in movie musicals during the 1950s and had several hit records during the period. Her song "Aba Daba Honeymoon" (featured in the 1950 film Two Weeks with Love as a duet with Carleton Carpenter) was a top-three hit in 1951. Her most high-profile film role was in Singin' in the Rain (1952) as Kathy Selden. In Bundle of Joy (1956) she appeared with her then-husband, Eddie Fisher.

Her recording of the song "Tammy" (from her 1957 film Tammy and the Bachelor) earned her a gold record, and was the best-selling single by a female vocalist in 1957. It was number one for five weeks on the Billboard pop charts. In the movie (the first of the Tammy film series) she co-starred with Leslie Nielsen.

In 1959 Reynolds recorded her first album for Dot Records, simply called Debbie, which included her own selection of 12 standards including "S’posin'", "Moonglow", "Mean To Me" and "Time After Time". Bing Crosby paid tribute to Reynolds in the sleeve notes accompanying the album thus:

Reynolds also scored two other top-25 Billboard hits with "A Very Special Love" (1958) and "Am I That Easy to Forget" (1960) — a pop-music version of a country-music hit made famous by both songwriters Carl Belew (in 1959), Skeeter Davis (in 1960), and several years later by singer Engelbert Humperdinck. During these years she also headlined in major Las Vegas showrooms.

Her starring role in The Unsinkable Molly Brown (1964) led to a nomination for the Academy Award for Best Actress. She then portrayed Jeanine Deckers in The Singing Nun (1966).

In what Reynolds has called the "stupidest mistake of my entire career", she made headlines in 1970 after instigating a fight with the NBC television network over cigarette advertising on her eponymous television series; NBC cancelled the show.

She continues to make appearances in film and television. From 1999 to its 2006 series finale, she played Grace Adler's ditzy mother Bobbi on the NBC sitcom Will & Grace (1998–2006), which earned her a Emmy Award nomination for Outstanding Guest Actress in a Comedy Series in 2000. She also plays a recurring role in the Disney Channel Original Movie Halloweentown film series as Aggie Cromwell. Reynolds made a guest appearance as a presenter at the 69th Academy Awards in 1997.

Reynolds has released several albums of both her vintage performances and her later recordings.

She is currently performing in her West End show Debbie Reynolds: Alive and Fabulous.