The play's first part, Millennium Approaches, was commissioned by the Center Theatre Group at the Mark Taper Forum, with which Kushner has a long association. It was first performed in Los Angeles as a workshop in May 1990 by the Center Theatre Group at the Mark Taper Forum.
Millennium Approaches received its world premiere in May 1991 in a production performed by the Eureka Theatre Company of San Francisco, directed by David Esbjornson. In London it premiered in a National Theatre production at the Cottesloe Theatre, directed by Declan Donnellan. Henry Goodman played Cohn, Nick Reding played Joe, Felicity Montagu played Harper, Marcus D'Amico played Louis, and Sean Chapman played Prior. Opening on 23 January 1992, the London production ran for a year. In November 1992 it visited Düsseldorf as part of the first Union des Théâtres de l'Europe festival.
The play's second part, Perestroika, was still being developed as Millennium Approaches was being performed. It was performed several times as staged readings by both the Eureka Theatre (during the world premiere of part one in 1991), and the Mark Taper Forum (in May 1992). It received its world premiere in November 1992 in a production by the Mark Taper Forum, directed by Oskar Eustis and Tony Taccone. In November 1993 it received its London debut at the National Theatre, in repertory with a revival of Millennium Approaches, again directed by Declan Donnellan. David Schofield played Cohn, Daniel Craig played Joe, Clare Holman played Harper, Jason Isaacs played Louis, Joseph Mydell played Belize and won the Olivier Award for Best Supporting Actor, and Stephen Dillane played Prior.
The entire two-part play debuted on Broadway at the Walter Kerr Theatre in 1993, directed by George C. Wolfe, with Millennium Approaches performed on May 4 and Perestroika joining it in repertory on November 23, closing December 4, 1994. The original cast included Ron Leibman, Stephen Spinella, Kathleen Chalfant, Marcia Gay Harden, Jeffrey Wright, Ellen McLaughlin, David Marshall Grant and Joe Mantello. Among the replacements during the run were F. Murray Abraham (for Ron Leibman), Cherry Jones (for Ellen McLaughlin), Dan Futterman (for Joe Mantello), Cynthia Nixon (for Marcia Gay Harden) and Jay Goede (for David Marshall Grant). Millennium Approaches and Perestroika were awarded, in 1993 and 1994 respectively, both the Tony Awards for Best Play and Drama Desk Awards for Outstanding Play.
The published script indicates that Kushner made a few revisions to Perestroika in the following year, thus officially completing the work in 1995. He made additional revisions to Perestroika during a run at the Signature Theatre in 2010. That production was directed by Michael Greif and featured Christian Borle as Prior, Zachary Quinto as Louis, Billy Porter as Belize, Bill Heck as Joe, Zoe Kazan as Harper, Robin Bartlett as Hannah, Frank Wood as Roy, and Robin Weigert as the angel.
A Canadian production by Soulpepper Theatre Company in 2013 and 2014 starred Damien Atkins as Prior Walter, Gregory Prest as Louis, Mike Ross as Joe, Diego Matamoros as Roy and Nancy Palk as Hannah, Ethel Rosenberg and the rabbi.
"Millennium Approaches" made its Edinburgh Fringe Festival debut, in a production by St Andrews-based Mermaids Theatre, in August 2013 to critical acclaim.
Asia premiered the play in its entirety in November 2014 at the Singapore Airlines Theatre.