The theater opened on October 2, 1918, with Jane Cowl's Information Please, and it initially hosted legitimate musical and dramatic productions.

[8] In the first two decades of the 20th century, eleven venues for Legitimate theatre were built within one block of West 42nd Street between Seventh and Eighth Avenues.

"[25][27] Elaine Louie of The New York Times wrote that the structure "proves that a glass building can have a 21st-century reason for its transparency and not just be a nod to old-fashioned Modernism".

[29] The Todd Haimes Theatre has a fan-shaped layout,[23][31] which led one critic to observe that "a whisper in the farthest part of the stage may be heard at the most remote seat".

[42][39] The upper stories contain a subscribers' lobby facing 43rd Street, as well as a smaller private lounge for large donors.

[59][60] In addition, Keister designed a renovation for the existing three-story building on 42nd Street, owned by Mary L. Cassidy, into an office structure.

[105] The next hit was the Marc Connelly and George S. Kaufman musical Helen of Troy, New York,[99][105] which opened in June 1923[106] and ran for several months before moving to the Times Square Theater.

[122] The play The Constant Nymph also opened at the Selwyn in 1926;[31][123] despite a successful West End run,[113] it stayed on Broadway for a relatively short 148 performances.

[127] By then, a lack of steady income led the Selwyn brothers to host shows on Sunday nights, when most other Broadway theaters did not operate.

Arch Selwyn hired Crosby Gaige to produce several shows, but none of them lasted for very long; one play, Ragged Army, ran for just two days.

[128] Arch Selwyn filed for bankruptcy shortly afterward; one of his debts was secured by a mortgage on the theater and office building.

[160] In August 1949, George Brandt suggested running live shows in their 42nd Street theaters,[165] though his father William was initially against it.

[175] By the late 1950s, the Selwyn was classified as a "move-over house", displaying features immediately after they ran at the Lyric, one of the street's two first-run theaters (the other being the New Amsterdam).

[183] The same year, the City University of New York's Graduate Center hosted an exhibition with photographs of the Selwyn and other theaters to advocate for the area's restoration.

[196] While the LPC granted landmark status to many Broadway theaters starting in 1987, it deferred decisions on the exterior and interior of the Selwyn Theatre.

[200] The Urban Development Corporation (UDC), an agency of the New York state government, then proposed redeveloping the area around a portion of West 42nd Street in 1981.

[208][209] In response, Brandt and Cine Theater Corp. sued the UDC, claiming that the moves shut out independent theatrical operators,[210][211] but a state court dismissed the lawsuit.

[215] From 1987 to 1989, Park Tower and Prudential hired Robert A. M. Stern to conduct a study on the Apollo, Lyric, Selwyn, Times Square, and Victory theaters on the north side of 42nd Street.

[230][234][235] Government officials hoped that development of the theaters would finally allow the construction of the four towers around 42nd Street, Broadway, and Seventh Avenue.

[239] After Disney committed to restoring the New Amsterdam Theatre in 1994, most of the other theaters around 42nd Street were quickly leased, but the Selwyn remained empty.

[246] The Roundabout Theatre Company had submitted a bid for one of the six theaters on 42nd Street, but its artistic director Todd Haimes initially rejected the area as being too rundown.

[247] Two months later, amid a rapid increase in the valuation of real estate along Times Square, the Criterion Center's owner notified Haimes that Roundabout's lease would be terminated in March 1999.

[34] The Wooster Group brought a limited production of Eugene O'Neill's The Hairy Ape to the Selwyn in April 1997[249][250] for an eight-week run.

[3] The development of the New 42nd Street Building forced the closure of the Grand Luncheonette in the Selwyn's lobby in October 1997; the restaurant had operated in Times Square for 58 years.

[20][256][257] The collapse destroyed several pieces of memorabilia in the Times Square visitor center, including pinball machines and sex-store advertisements.

[260] In August 1998, the DOB found that the Big Apple Wrecking and Construction Corporation, a contractor for the E-Walk project, was liable for the Selwyn Building's collapse.

[263] The New York State Council on the Arts, which had pledged funding for the Selwyn's restoration, instead allocated the money toward a new design for the New 42nd Street Building.

[269] Donors could pay $5,000 for a plaque affixed to one of the orchestra-level seats; $75,000 for a bathroom; $375,000 for the orchestra pit; and $10 million for naming rights to the entire theater.

[167] Typically, the American Airlines hosted two to five Broadway productions per season due to Roundabout's subscription format; most shows ran for fewer than 100 performances.

[281][283] The American Airlines opened the 2004–2005 season with a revival of the play Twelve Angry Men,[289] which was extended several times and became Roundabout's longest-running show at the theater.