He developed a stand-up comedy act, starred as the Yogi in the Broadway musical revue The Nervous Set,[5] and performed briefly with an improv company in Greenwich Village with fellow Compass alumni Mark and Barbara Gordon.

Close also worked with John Brent to record the classic Beatnik satire album How to Speak Hip, a parody of language-learning tools that purported to teach listeners the secret language of the "hipster".

[6] In 1960 Close moved to Chicago, his home base for much of the rest of his life, to perform and direct at Second City, but was fired due to substance abuse.

He spent the latter half of the 1960s in San Francisco where he was the house director of improv ensemble The Committee, featuring performers such as Gary Goodrow, Carl Gottlieb, Peter Bonerz, Howard Hesseman and Larry Hankin.

In the early 1980s he served as "house metaphysician" at Saturday Night Live; for many years, a significant percentage of the show's cast were Close protégés.

He spent the mid-to-late 1980s and 1990s teaching improv, collaborating with Charna Halpern at Yes And Productions and the ImprovOlympic Theater with Compass Players producer, David Shepherd.

[8] During this period, Close also appeared in several movies; he portrayed corrupt alderman John O'Shay in The Untouchables[9] and an English teacher in Ferris Bueller's Day Off.

In the 2020 documentary For Madmen Only: The Stories of Del Close, he is filmed on stage saying to the improv actors and audience, “My father was a spectacular suicide.

Charna Halpern, Close's long-time professional partner and the executor of his will, conveyed a skull that she claimed was his, in a high-profile televised ceremony on July 1, 1999.

[17] Halpern stood by her story at the time but admitted three months later, in a The New Yorker interview, that she had purchased the skull from a local medical supply company.

[18][19] Bill Murray organized an early 65th birthday party and wake, shortly before Del's anticipated death as he lay on his deathbed in a Chicago hospital, memorialized in a two-part video.

[21] In 2002, Cesar Jaime and Jeff Pacocha produced and directed a film composed of interviews with former students, friends, and collaborators of Del Close.

[27] There have been a number of different individuals that have claimed for themselves, or been attributed with, giving Hubbard the suggestion of turning Scientology into a religion in order to make a lot of money.

[29] The feature was an account of O'Donnell's visits at Del's Chicago apartment as well as recounting highlights of their time spent at CrossCurrents, the theater that housed both their comedy groups.