She was born out of wedlock, as would have to be the case given the laws regarding miscegenation at the time, in tiny North, South Carolina, but jokes about the fact that many audiences assume her to be from somewhere more exotic. Her hits include "Let's Do It", "C'est Si Bon", "Just an Old Fashioned Girl", "Monotonous", "Love for Sale", "I'd Rather Be Burned as a Witch", "Uska Dara", "Mink, Schmink", "Under the Bridges of Paris", and arguably her most recognizable hit, the sexily sung Christmas song "Santa Baby". Kitt's unique style was enhanced as she became fluent in French during her years performing in Europe. She dabbled in other languages as well, which she demonstrates with finesse in many of the live recordings of her cabaret performances.

Eartha Kitt got her start as a member of the Katherine Dunham Company and made her film debut with them in Casbah (1948). In 1950, Orson Welles gave her her first starring role: as Helen of Troy in his staging of Dr. Faust. A few years later, she was cast in the revue New Faces of 1952 introducing "Monotonous", "C'est Si Bon" and "Santa Baby", three songs with which she continues to be identified. During her run, 20th Century-Fox filmed a version of the play. Orson Welles and Kitt allegedly had a torrid affair during her run in Shinbone Alley, which earned her the nickname by Welles as "the most exciting girl in the world". In 1958, Kitt made her feature film debut opposite Sidney Poitier in The Mark of the Hawk. Throughout the rest of the 1950s and early 1960s, Kitt would work on and off in film, television and on nightclub stages. In the late 1960s television series Batman, she played Catwoman in succession to Julie Newmar. This role would be the role she would best be remembered for, owing to her purring drawl.

In 1968, however, Kitt encountered a substantial professional setback after she made anti-war statements during a White House luncheon that reportedly made first lady Lady Bird Johnson weep uncontrollably. Professionally exiled from the U.S., she devoted her energies to overseas performances before returning to New York in a triumphant turn in the Broadway spectacle Timbuktu! (a version of the perennial Kismet set in Africa) in 1978.

In 1984, she returned to hit music with a dance song, Where Is My Man; she found new audiences in nightclubs across the country, including a whole new generation of gay male fans, and she responded by frequently giving benefit performancess in support of HIV/AIDS organizations.

In 2000, Kitt again returned to Broadway in the short but notable run of the revival of the 1920s-themed, The Wild Party, opposite Mandy Patinkin and Toni Collette. In 2003, she replaced Chita Rivera in Nine. In recent years she has also appeared as the Wicked Witch in an arena version of The Wizard of Oz.

One of her more unusual roles was as Kaa the python in a 1994 BBC Radio adaptation of The Jungle Book. Kitt lent her distinctive voice to the role of Yzma in The Emperor's New Groove and is currently doing other voiceover work such as the voice of Queen Vexus on the animated TV series My Life as a Teenage Robot.

In recent years, Kitt's annual appearances in New York have made her a fixture of the Manhattan cabaret scene. She takes the stage at venues such as The Ballroom and, more recently, the Café Carlyle to explore and define her highly stylized image, alternating between signature songs (such as Old Fashioned Millionaire), which emphasize a witty, mercenary world-weariness, and less familiar repertoire, much of which she performs with an unexpected ferocity and bite that present her as a survivor with a seemingly bottomless reservoir of resilience — her version of Here's to Life, frequently used as a closing number, is a sterling example of the latter. This side of her later performances is reflected in at least one of her recordings, Thinking Jazz, which preserves a series of performances with a small jazz combo that took place in the early 1990s in Germany and which includes both standards (Smoke Gets in Your Eyes) and numbers (such as Something May Go Wrong) that seem more specifically tailored to her talents; one version of the CD includes as bonus performances a fierce, angry Yesterdays and a live take of C'est Si Bon that good-humoredly satirizes her sex-kitten persona.