Ebersole was born in Winnetka, Illinois, where she attended New Trier High School. She attended MacMurray College in Jacksonville, Illinois.

She appeared in Ryan's Hope in 1977 and 1980, and later was part of the cast of Saturday Night Live, acting as Weekend Update co-anchor with Brian Doyle-Murray and at times impersonating Mary Travers, Cheryl Tiegs, Barbara Mandrell, Princess Diana, and Rona Barrett. Following SNL, she appeared in One Life to Live and Valerie. She played the title role in the short-lived television series Rachel Gunn, R.N. and has guest-starred on Will & Grace, The Nanny, Just Shoot Me, Murphy Brown, Ally McBeal, Samantha Who, Boston Legal, The Colbert Report, and Royal Pains, among others. She also appeared in the 1993 television adaptation of Gypsy starring Bette Midler. She will co-star in the upcoming TV Land sitcom Retired at 35 in January 2011.

Ebersole's films have included Amadeus (1984), Mac and Me (1988), My Girl 2 (1994), Richie Rich (1994), Black Sheep (1996), 'Til There Was You (1997), and My Favorite Martian (1999).

Ebersole has found considerable success on stage. Off-Broadway she has appeared in Three Sisters and Talking Heads, and her Broadway credits include On the Twentieth Century, the 1979 revival of Oklahoma!, the 1980 revival of Camelot, the 2000 revival of Gore Vidal's The Best Man, the 2001 revival of 42nd Street (for which she won the Tony Award for Best Leading Actress in a Musical), the 2002 revival of Dinner at Eight (for which she was nominated for another Tony Award), and Steel Magnolias.

In 2006, Ebersole took the dual roles of Edith Ewing Bouvier Beale ("Big Edie") and Edith Bouvier Beale ("Little Edie") in Grey Gardens, a musical based upon the film of the same name. After a sold-out off-Broadway run, Ebersole remained with the roles when the production moved to Broadway later in the year. For this role, she won her second Tony Award for Best Leading Actress in a Musical. Most recently she appeared as Elvira in the 2009 revival of the Noël Coward comedy Blithe Spirit.

Ebersole has been married twice, to Peter Bergman and to her present spouse Bill Moloney, with whom she has adopted three children, Elijah, Mae Mae, and Aron. She is the aunt of actress Janel Moloney through marriage. She currently lives in Maplewood, New Jersey, with her family.

Marla Schaffel (2001) · Sutton Foster (2002) · Marissa Jaret Winokur (2003) · Donna Murphy (2004) · Victoria Clark (2005) · Christine Ebersole (2006) · Audra McDonald / Donna Murphy (2007) · Patti LuPone (2008) · Allison Janney (2009) · Catherine Zeta-Jones / Montego Glover (2010)

Complete list · (1975-2000) · (2001-present)

Christine Ebersole (2001) · Sutton Foster (2002) · Marissa Jaret Winokur (2003) · Idina Menzel (2004) · Victoria Clark (2005) · LaChanze (2006) · Christine Ebersole (2007) · Patti LuPone (2008) · Alice Ripley (2009) · Catherine Zeta-Jones (2010)

Complete list · (1948-1975) · (1976-2000) · (2001-present)