Under the leadership of Founding Artistic Director Elysabeth Kleinhans and Executive Producer Peter Tear, 59E59 Theaters opened its inaugural season in February 2004 with a production of The Stendhal Syndrome produced by then resident company, Primary Stages, in the largest of its three spaces, Theater A.

Shortly following, in April 2004, the other two spaces, Theater B and Theater C opened their doors with productions of Sun Is Shining, by the ground breaking British-Chinese Mu Lan Theatre Company, and My Arm, Tim Crouch's critically-acclaimed hour-long solo show from the Edinburgh Festival Fringe, during the Theaters' first annual Brits Off Broadway—a season dedicated to premiering new work by Off Broadway-style UK companies.

In 2017, Elysabeth Kleinhans and Peter Tear stepped down from their roles, and Val Day, a longtime agent with William Morris and ICM, was appointed as Artistic Director.

The Season usually takes place during the months of April, May, and June and comprises between 6 and 8 productions across the three theater spaces.

"[3] Past seasons have seen work by Richard Bean (One Man, Two Guvnors) and Alan Ayckbourn (The Norman Conquests, Bedroom Farce) amongst other notable British playwrights.