Architect Henry B. Herts designed the Booth and its companion Shubert Theatre as a back-to-back pair sharing a Venetian Renaissance-style façade. Named in honor of famed 19th-century American actor Edwin Booth, brother of John Wilkes Booth, the theater's 783-seat auditorium was intended to provide an intimate setting for dramatic and comedy plays. It opened on October 16 1913 with Arnold Bennett's play The Great Adventure.
The venue was the second New York City theatre to bear this name. The first was built by Booth himself in 1869 on the corner of 23rd Street and 6th Avenue.
The Booth Theatre appeared in the West Wing episode Posse Comitatus. It hosted a fictitous charity performance of War of the Roses which an equally fictitious President Bartlett attended while pondering the planned assassination of the Quamari Defence Minister.