Chenoweth sang gospel music as a child in Oklahoma and studied opera before deciding to pursue a career in musical theatre. In 1997, she made her Broadway debut in Steel Pier, winning a Theatre World Award, before appearing in You're a Good Man, Charlie Brown and Wicked. Her other Broadway roles were in The Apple Tree in 2006, Promises, Promises in 2010 and On the Twentieth Century in 2015, for which she received another Tony Award nomination. She has also appeared in five City Center Encores!, Off-Broadway and regional theatre productions.
Chenoweth had her own sitcom, Kristin, in 2001, and has guest-starred on many shows, including Sesame Street and Glee, for which she was nominated for Emmy Awards in 2010 and 2011. In films, she has played mostly character roles, such as in Bewitched (2005), The Pink Panther (2006) and RV (2006). She has played roles in made-for-TV movies, such as Descendants (2015); done voice work in animated films such as Rio 2 (2014) and The Peanuts Movie (2015) along with the animated TV series Sit Down, Shut Up and BoJack Horseman; hosted several award shows; and released several albums of songs, including A Lovely Way to Spend Christmas (2008), Some Lessons Learned (2011), Coming Home (2014), The Art of Elegance (2016) and For the Girls (2019). Chenoweth also wrote a 2009 memoir, A Little Bit Wicked.