Clark was born and raised in Dallas, Texas, the daughter of Lorraine and Banks Clark. She studied the piano and attended the Hockaday School, an all-girls school in Dallas. She attended the Interlochen Arts Academy before going to Yale University, graduating in 1982. At Yale, at the age of eighteen, she sang the role of Mabel in Gilbert and Sullivan's comic opera The Pirates of Penzance. She also sang the title role in Gilbert and Sullivan's Patience, and directed a production of Ruddigore for the Yale Gilbert & Sullivan Society. After college, Clark studied at New York University's Musical Theatre Master's Program as a stage director and began to direct operas and musicals professionally. Although she continues to direct, she has primarily focused on singing and acting.
Clark's stage work includes roles in the Broadway musicals Guys and Dolls (1992–93), A Grand Night for Singing (1993–94), How to Succeed in Business Without Really Trying (1995–96, as Smitty), Titanic (1997–99, creating the role of Alice Beane), Cabaret (1999–2000, as Fraulein Kost) and Urinetown (2003, as Penelope Pennywise), as well as numerous roles Off-Broadway, in national tours and in regional theatre. She played Doris MacAfee in the City Center Encores! production of Bye Bye Birdie in 2004.
In 2005, Clark won the Tony Award for Best Leading Actress in a Musical, a Drama Desk Award, an Outer Critics Circle Award, and the Joseph Jefferson Award for her performance in the musical The Light in the Piazza (2005–06). Broadway.com commented on Clark's performance, "What is indisputable is that Victoria Clark has created a character for the ages. Lucas has done a superb job in fleshing out Margaret within the confines of a musical-theater libretto, and Clark responds with consummate precision and grace. Calling hers the musical performance of the year would be accurate. It would also be a drastic understatement." She appeared as former showgirl Sally Durant Plummer in the Encores! staged concert presentation of Follies in February 2007 at City Center. She next created the role of Margaret Brennan in The Marriage of Bette and Boo Off-Broadway in 2008 for the Roundabout Theatre Company.

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