Topdog/Underdog opened Off-Broadway at the Public Theater on July 26, 2001 and closed on September 2, 2001. Directed by George C. Wolfe, Don Cheadle (as Booth) and Jeffrey Wright (as Lincoln) starred. The play opened on Broadway at the Ambassador Theatre on April 7, 2002 and closed on August 11, 2002. Cheadle was replaced by Mos Def; direction was by George C. Wolfe. The play transferred to London at the Royal Court Theatre in 2003, with the same Broadway cast, and directed by Wolfe.
In September 2012, Topdog/Underdog was produced by the Two River Theater Company in Red Bank, New Jersey.
A 2011 production at the Shaw Festival in Canada starred Kevin Hanchard as Booth and Nigel Shawn Williams as Lincoln. This production had a second run at The Theatre Centre in Toronto later in the same year through Obsidian Theatre Company. Hanchard and Williams were both nominated for Outstanding Performance by a Male in a Principal Role – Play at the 2012 Dora Mavor Moore Awards; Williams won the award. Director Philip Akin also won the Dora for Outstanding Direction of a Play/Musical.
Parks commented on the meaning of the play: "I think the meaning of the play isn’t just confined to a man's experience... I think it's about what it means to be family and, in the biggest sense, the family of man, what it means to be connected with somebody else." She noted that the play speaks to "who the world thinks you’re going to be, and how you struggle with that."