Since February 2001, she has served as the co-host of Live with Regis and Kelly (a morning talk show), alongside Regis Philbin. She is also known for her acting on All My Children and Hope & Faith, both television series on ABC.

While attending Eastern High School in Voorhees Township, New Jersey, Kelly Ripa began acting in high school plays. This led to roles at local theaters and a regular spot on the USA Network's Dance Party USA – an afternoon teen music program. She was then cast as gothic teen turned suffering heroine, Hayley Vaughan, on the soap opera All My Children. Starting on the show in 1990, the character of Hayley quickly drew a large following.

In early 1995 her character was paired with Mark Consuelos' character, Mateo Santos. A romance blossomed between the castmates, with Ripa and Consuelos eloping in 1996. Eventually, they had three children — Michael Joseph Consuelos, born June 2, 1997; Lola Grace Consuelos, born June 16, 2001; and Joaquin Antonio Consuelos, born February 24, 2003. In a mutual decision, the couple left All My Children in December 2002.

In September 2003, Ripa was a co-star (with Faith Ford) on her first sitcom, Hope & Faith. She portrayed Faith, a former soap star whose character is killed off and who moves in with her sister Hope's family, creating havoc for the family and often antagonizing Hope and her husband, Charlie. Hope & Faith was not renewed for a fourth season in May 2006 after the 2005-2006 season saw a significant decline in ratings.

On Saturday Night Live skits about Live with Regis and Kelly, the role of Kelly Ripa is played by Amy Poehler. When Ripa hosted SNL in November 2003, in the Live with Regis and Kelly skit, Poehler appeared as Ripa and Ripa as Angelina Jolie. In another skit, Ripa spoofed the ubiquitous hair coloring ads in which she has appeared (in this skit, Ripa prefers Tressant Suprême because a main ingredient is crack cocaine, thus explaining her stereotypical "peppy" persona). In another episode, she had a cameo as herself in a skit about Bangkok, Thailand with Ben Affleck. She also appeared in an opening skit with Steve Martin as the host, where they have dinner until Martin finds out that Alec Baldwin is about to host the show again.

She has also made fun of herself on Family Guy, voicing herself. In the episode "Family Guy Viewer Mail #1", Peter Griffin found a genie in a beer bottle and his first wish was to see Kelly Ripa behind the scenes. The genie opened a magic window onto Ripa's Live with Regis and Kelly dressing room, showing Ripa ripping off her human face to show an ugly alien face, then going to a tied-up human, removing his heart and eating it.

Ripa won three Soap Opera Digest Awards for playing Hayley on All My Children in 1996, 1998 & 2000. She has been nominated for 8 Daytime Emmy Awards. Three of these nominations were for playing Hayley on All My Children, and 5 were for performing hosting duties alongside Regis.