De Shields was born on January 12, 1946, in Dundalk, Maryland, to Mary Gunther and John De Shields. He was raised in Baltimore, Maryland, as the ninth of eleven children. De Shields obtained his high school diploma at Baltimore City College in 1964, then attended Wilmington College, where he starred in a production of Lorraine Hansberry’s A Raisin in the Sun. He then transferred colleges and earned his B.A. degree in English literature from the University of Wisconsin-Madison in 1970.

De Shields began his professional career in the 1969 Chicago production of Hair, which led to a role in The Me Nobody Knows and participation in Chicago’s Organic Theater Company. He performed in a number of off-off-Broadway productions at La MaMa Experimental Theatre Club in the East Village of Manhattan during the 1970s, 1980s, and early 1990s. These included Ken Rubenstein’s Sacred Guard (1973), Lamar Alford’s Thoughts (1974), and the Cotton Club Gala with music by Aaron Bell and directed by Ellen Stewart (1985). He co-wrote (with Judith Cohen) and directed an evening of songs called Judith and the Cohen Sisters in Midnight in Manhattan at La MaMa in September/October 1984. He directed a production of Chico Kasinoir’s The Adventures of Rhubarb: The Rock and Roll Rabbit in 1985 and a production of his own work, Saint Tous, to celebrate Black History Month at La MaMa in February 1991.

After choreographing two Bette Midler musicals, De Shields returned to Broadway to perform in the musical revue Ain’t Misbehavin’ in 1978. The original production ran for over 1,600 shows and De Shields earned a 1978 Drama Desk nomination for his performance. Three years later, he returned to Broadway to perform in Stardust: The Mitchell Parrish Musical, a musical revue featuring the lyricist’s work with Hoagy Carmichael, Benny Goodman, Duke Ellington, and Leroy Anderson.

De Shields has appeared on television on Another World, Cosby, Sex and the City, Great Performances, Lipstick Jungle, Law & Order, and Law & Order: Special Victims Unit. He won an Primetime Emmy Award for Outstanding Individual Achievement for his performance in the 1982 NBC broadcast of Ain’t Misbehavin’, and played Tweedledum in a 1983 televised production of Alice in Wonderland that also featured Eve Arden, Richard Burton, Colleen Dewhurst, James Coco, Kaye Ballard, and Nathan Lane. Most recently, De Shields appeared in John Mulaney’s John Mulaney & the Sack Lunch Bunch in which he sang “Algebra Song!” The comedy/musical/variety special was released on Netflix on December 24, 2019. Since 2020, he plays the role of Chubby, a recurring character, in the television series Katy Keene on The CW.

In 1984, De Shields wrote, choreographed, directed, and starred in André De Shields’ Haarlem Nocturne, a Broadway musical revue featuring standards from the American songbook, pop hits from the early 1960s, and De Shields’ own songs. The revue was produced at the Latin Quarter and at La MaMa (with music by Marc Shaiman). He appeared in a revival of Ain’t Misbehavin’ in 1988, and next appeared on Broadway in 1997 as the Jester in Play On!, a musical based on Ellington’s songs. De Shields earned Tony and Drama Desk nominations for his performance.

In 1991, De Shields received his M.A. degree in African American studies from New York University’s Gallatin School of Individualized Study, where he now serves as an adjunct professor.

In 2000, De Shields originated the role of Noah “Horse” T. Simmons in the Terrence McNally / David Yazbek musical adaptation of the film The Full Monty. As with Play On!, De Shields earned both Tony and Drama Desk nominations for this performance. In 2004, he appeared in the Broadway production of Mark Medoff’s Prymate at the Longacre Theatre. In 2008, he received a Drama Desk nomination for his performance in an off-Broadway production of Langston Hughes’ Black Nativity. In 2009, he appeared on Broadway opposite Joan Allen and Jeremy Irons in Impressionism. The play ran through May 2009 at the Gerald Schoenfeld Theater.

De Shields has portrayed Barrett Rude Sr. in The Fortress of Solitude, the musical based on Jonathan Lethem’s novel The Fortress of Solitude, since its inception in 2012 at Vassar College. The Fortress of Solitude premiered at the Dallas Theater Center in spring 2014, and the off-Broadway production of The Fortress of Solitude, co-produced with The Public Theater, ran through November 2014. De Shields, Lillias White, Stefanie Powers, and Georgia Engel starred in the new musical Gotta Dance, directed and choreographed by Jerry Mitchell. The musical began performances on December 13, 2015, at Chicago’s Bank of America Theatre and ran through January 17, 2016. He is currently on Broadway playing Hermes in Hadestown, which began previews on March 22, 2019, at the Walter Kerr Theatre. He received the Tony Award for Best Featured Actor in a Musical for Hadestown on his third nomination.

De Shields’ regional theatre credits include Play On!, The Full Monty, Waiting For Godot, The Man Who Came to Dinner, Death of a Salesman, Dusyanta: A Tale of Kalidasa, The Gospel According to James, and Camino Real. In 2013, he portrayed Akela and King Louie in the world premiere of Mary Zimmerman’s adaptation of Rudyard Kipling’s The Jungle Book, a co-production of the Goodman Theatre and Huntington Theatre Company. De Shields received his 3rd Jeff Award (Outstanding Achievement in the category of Actor in a Supporting Role – Musical) for his role as King Louie, and garnered an Elliot Norton Awards nomination for Outstanding Musical Performance by an Actor as well as an IRNE Awards nomination for Best Supporting Actor – Musical.

De Shields is openly gay. He revealed in February 2020 that he has been living with HIV for over thirty years.