She first gained fame in the 1950s for her improvisational comedy routines with Mike Nichols before transitioning her career, regularly breaking the mold as a writer and director of several critically acclaimed films.

May later earned acclaim writing the screenplays for Warren Beatty's Heaven Can Wait (1978), and Mike Nichols' The Birdcage (1996) and Primary Colors (1998).

Mike Nichols, who was then an actor in the school's theatrical group, remembers her coming to his philosophy class, making "outrageous" comments, and leaving.

The director Paul Sills brought May to Nichols and said, "Mike, I want you to meet the only other person on the campus of the University of Chicago who’s as hostile as you are: Elaine May."

Bobbi Gordon, an actor, remembers that she was often the center of attention: "The first time I met her was at Compass... Elaine was this grande dame of letters.

British actor Richard Burton, who was married to Elizabeth Taylor at the time, agreed with that impression after he first met May while he was starring in Camelot on Broadway.

[15]: 331 Nichols was personally asked to leave the Compass Players in 1957 because he and May became too good, which threw the company off balance, noted club manager Jay Landsman.

[15]: 346  Their relatively brief time together as comedy stars led New York talk show host Dick Cavett to call their act "one of the comic meteors in the sky".

Producer David Shepherd notes that she accomplished that partly by not choosing traditional 1950s female roles for her characters, which were often housewives or women working at menial jobs.

The event, titled "Together Again for McGovern," also featured two musical groups that had recently broken up, Simon and Garfunkel and Peter, Paul and Mary, as well as singer Dionne Warwick.

[citation needed] May has also acted in comedy films, including Enter Laughing (1967), directed by Carl Reiner, and Luv (1967), costarring Peter Falk and Jack Lemmon.

May received a Golden Globe nomination for her portrayal of the shy botanist in the project from which she fought studio exec Robert Evans, unsuccessfully, to have her name removed.

[citation needed] May ended up in a legal battle with Paramount Pictures over post-production costs, at one point hiding reels of the film in her husband's friend's Connecticut garage and later suing the company for $8 million for breach of contract.

[28][29] In Herbert Ross's California Suite (1978), written by Neil Simon, she was reunited with A New Leaf co-star Walter Matthau, playing his wife Millie.

The advance publicity was largely negative[33] and, despite some positive reviews from the Los Angeles Times and The Washington Post, the film was a box office disaster.

[34][35] The film Ishtar has been positively re-evaluated in the 21st century by multiple publications including the Los Angeles Times, Slate, Indiewire, and The Dissolve.

"[41] May acted in the film In the Spirit (1990), in which she played a "shopaholic stripped of consumer power"; Robert Pardi has described her portrayal as a "study of fraying equanimity [that] is a classic comic tour de force.

[43] May reunited with her former comic partner, Mike Nichols, for the 1996 film The Birdcage, an American adaptation of the classic French farce La Cage aux Folles.

"[44] Nearly 15 years later, Allen ended up casting her to play his wife, Kay Munsinger, in his Amazon limited series, Crisis in Six Scenes, which was released in 2016.

[46] In 2002, Stanley Donen directed her musical play Adult Entertainment with Jeannie Berlin and Danny Aiello at Variety Arts Theater in Manhattan.

A table reading of the script for potential investors included such actors as Christopher Walken, Charles Grodin, Ron Rifkin, and Jeannie Berlin.

[52] That same year, she returned to acting, her first role since 2000, starring alongside her friend Woody Allen in his series Crisis in Six Scenes on Amazon Prime,[53] Tim Goodman of The Hollywood Reporter praised their chemistry together writing, "The best episodes are the last two, when Crisis in Six Scenes becomes a full-blown farce and we get to see Allen and May playing accidental aging radicals, shuffling around Brooklyn".

[54] In 2018, aged 86, May returned to Broadway after 60 years in a Lila Neugebauer-directed revival of Kenneth Lonergan's play The Waverly Gallery opposite Lucas Hedges, Joan Allen, and Michael Cera.

[58] Nichols and May created a new "Age of Irony" for comedy, which showed actors arguing contemporary banalities as a key part of their routine.

"[15]: 324 In Vanity Fair, Woody Allen declared, "Individually, each one is a genius, and when they worked together, the sum was even greater than the combination of the parts—the two of them came along and elevated comedy to a brand-new level.

"[15]: 324 In an interview with Pitchfork Magazine, standup comedian John Mulaney described Mike Nichols & Elaine May Examine Doctors (1961) as one of his favorite comedy albums of all time.

May's work as a director has been given a closer look in recent years with David Hudson, a writer for The Criterion Collection declaring her as a "criminally underappreciated moviemaker".

[45] On stage, May won the Tony Award for Best Actress in a Play for her performance as Gladys in the Broadway revival of Kenneth Lonergan's The Waverly Gallery in 2019.

[72] May was awarded the National Medal of Arts for her lifetime contributions to American comedy by President Barack Obama, in a ceremony in the White House on July 10, 2013.

She was awarded for her "groundbreaking wit and a keen understanding of how humor can illuminate our lives, Ms. May has evoked untold joy, challenged expectations, and elevated spirits across our Nation.