Seldes was born in New York City, the daughter of Alice "Amanda" Wadhams Hall, a socialite, and Gilbert Seldes, a journalist, author, and editor. Her uncle was journalist George Seldes. Seldes's paternal grandparents were Russian Jewish immigrants, and her mother was from a "prominent WASP family," the "Episcopalian blue-blooded Halls." Seldes had a brother, Timothy, and grew up in a creative environment, studying acting at the Neighborhood Playhouse. Her mother's sister, Marian Wells Hall (died 1972), was a prominent American interior decorator.

Trained for the stage, Seldes made her Broadway theatre debut in 1948 in a production of Medea. She went on to an illustrious career in which she has earned five Tony Award nominations, winning her first time out in 1967 for A Delicate Balance. In addition to performing in live theatre, Seldes began acting in television in 1952 in a Hallmark Hall of Fame production that marked the first of many guest star roles. She also has performed in a number of motion pictures and in radio plays. In the mid-sixties, Seldes recorded five albums for Folkways Records of famous works of literature. Between 1974 and 1982, she appeared in 179 episodes of the CBS Radio Mystery Theater. In 1992 she appeared as Murphy Brown's eccentric Aunt Brooke.

She has a daughter, Katharine, by her first marriage to Julian Claman. They were divorced in 1961. Seldes says that the marriage to Claman was violent. “If I sound a little vague about that marriage, it’s because I don’t understand the person in it. Me. I literally didn’t know that people could be abusive." Seldes left the marriage after her father noticed marks on Seldes' face. Seldes was married to screenwriter/playwright Garson Kanin from 1990 until his death in 1999.

At various times, Sanford Meisner, Katherine Cornell and Martha Graham taught Marian Seldes. Actor Laura Linney says, "Marian is our touchstone to those theatrical ancestors. She provides an inspiration that makes you want to reach outside of yourself to something more potent and powerful." Marian Seldes was a member of the Juilliard School of Performing Arts from 1969 to 1972. Some of Marian Seldes' students include Robin Williams, Kelsey Grammer, Kevin Kline, William Hurt and Patti LuPone. In 2002 Marian Seldes began teaching at Fordham University, Lincoln Center.

Seldes appeared in every one of the 1,809 Broadway performances of Ira Levin's play Deathtrap - a feat that earned her a mention in the Guinness Book of World Records as "most durable actress." Seldes is also well-known for her readings of short stories in the "Selected Shorts" series hosted by Isaiah Sheffer at New York City's Symphony Space. Marian Seldes is the recipient of a 2010 Antoinette Perry ("Tony") Lifetime Achievement Award.

Guest Starred on Sex and the City season 1 as Mr Big's Mother.

Played Christie Smith in Season 1, Episode 6 (The Bride) of Have Gun Will Travel.

Theodore Bikel: "Songs of Songs" and other Biblical Prophecies" featuring Marian Seldes as Shulamite. (1964))

Patricia Neal (1947) · Shirley Booth (1949) · Maureen Stapleton (1951) · Marian Winters (1952) · Beatrice Straight (1953) · Jo Van Fleet (1954) · Patricia Jessel (1955) · Una Merkel (1956) · Peggy Cass (1957) · Anne Bancroft (1958) · Julie Newmar (1959) · Anne Revere (1960) · Colleen Dewhurst (1961) · Elizabeth Ashley (1962) · Sandy Dennis (1963) · Barbara Loden (1964) · Alice Ghostley (1965) · Zoe Caldwell (1966) · Marian Seldes (1967) · Zena Walker (1968) · Jane Alexander (1969) · Blythe Danner (1970) · Rae Allen (1971) · Elizabeth Wilson (1972) · Leora Dana (1973) · Frances Sternhagen (1974) · Rita Moreno (1975)

Complete list: (1947–1975) · (1976–2000) · (2001–present)