She has received more Tony Award nominations (ten) and wins (five) than any other performer and in 1966 won the Sarah Siddons Award for her work in Chicago theatre.

Harris's screen debut was in 1952 in The Member of the Wedding, for which she was nominated for the Academy Award for Best Actress. She had created the role on Broadway. She has also appeared in such seminal films as East of Eden, Reflections in a Golden Eye, and Requiem for a Heavyweight.

Harris appeared as the star of The Haunting, director Robert Wise's 1963 screen adaptation of a novel by Shirley Jackson. Production took place starting in October, 1962, at MGM Borehamwood studios, with location work near Stratford-upon-Avon. Another cast member recalled Harris maintaining a social distance from the other actors while not on set, later explaining that she had done so as a method of emphasizing the alienation from the other characters experienced by her character in the film.

She reprised her Tony-winning role as Mary Todd Lincoln in 1973's play Last of Mrs. Lincoln to the film version, which appeared in 1976.

Besides her Academy Award nomination and her Tony Awards, Harris has won three Emmy Awards and has been nominated eleven times.

On December 5, 2005, she was named a Kennedy Center Honoree. She was honored along with singer Tony Bennett, ballerina Suzanne Farrell, singer Tina Turner, and actor Robert Redford. At a White House Ceremony, President George W. Bush remarked, "It's hard to imagine the American stage without the face, the voice, and the limitless talent of Julie Harris. She has found happiness in her life's work, and we thank her for sharing that happiness with the whole world."

On television, she is best known for her role as Lilimae Clements on the soap opera Knots Landing, a role she played as a recurring character from 1980 to 1981 and as a series regular from 1981 to 1987.

She lives in Chatham, Cape Cod, and was a friend to the late illustrator Edward Gorey and neighbor to the late Shirley Booth, whom she visited frequently. While living in New England, she has continued to work and has narrated five historical documentaries by Christopher Seufert and Mooncusser Films and is active as a director on the board of the independent Wellfleet Harbor Actor's Theater. She has also done extensive voice over work for documentary maker Ken Burns.

She is thrice divorced with one son, Peter Gurian.

She has survived (despite her seemingly frail physique): breast cancer, a bad fall requiring surgery, and a stroke.