The 23-story hotel was designed by Everett F. Murgatroyd and Palmer H. Ogden in a blend of the Italian Renaissance, Late Gothic Revival, and Islamic styles.

The facade consists of salmon-colored brick, with limestone and terra cotta decorations, and is divided into a three-story base, a 15-story shaft, and a five-story tower.

When the Barbizon was built, it contained various amenities for its residents, including a gymnasium, private library, solarium, swimming pool, and Turkish bath.

Between the 1930s and the 1960s, the hotel hosted numerous clubs, and entities such as Mademoiselle magazine, the Katharine Gibbs Secretarial School, and the Ford Modeling Agency rented rooms there.

[11] On these elevations, the intermediate stories contain cruciform niches and projecting bricks, while the setbacks are marked by arched Gothic Revival–style corbel tables and trellises.

On the north and west elevations, the center of the 21st story contains round windows, which flank a double-height arched dormer with a gable and a brick and stone frame.

[19] The building contained various amenities for its residents, including a gymnasium, private library, solarium, swimming pool, and Turkish bath.

[51][55] In the years following World War I, there had been a great increase in the number of female college students, which had long been underrepresented in higher education compared to their male counterparts.

[22][56][57] However, there was a shortage of housing units available in New York City due to inflation and rent controls implemented during World War I, and the few available apartments tended to be overly expensive.

[22] In January 1926, the trustees of Temple Rodeph Sholom voted to sell their 92-by-120-foot (28 by 37 m) site on the southeast corner of Lexington Avenue and 63rd Street to the Amri Realty Company, which planned to build an apartment hotel there.

[59][60] Amri's president, Bernard Reich,[61][62] hired Emery Roth to design the new building since, at the time, the surrounding neighborhood did not have any apartment hotels.

[61] Amri sought to sell the synagogue and the Lexington Avenue structure to the Allerton Hotel chain, headed by William Silk, by September 1926.

[80] Various events such as organ recitals, contract bridge games, and afternoon tea were provided for residents, and the hotel even had its own social director.

[74] In addition to the Wellesley Club of New York and Four Arts Wing, the Barbizon contained the clubhouses for alumni of Mount Holyoke College and Cornell University.

[90][91] The Arts Council of New York moved to the Barbizon's mezzanine shortly after it opened,[74][92] and the Association of Junior Leagues of America relocated its national headquarters to the building in mid-1928.

[98] A bondholders' committee led by real-estate agent Lawrence B. Elliman bought the Barbizon at an auction in July 1932,[99] bidding $460,000 for the hotel and $28,000 for the furnishings.

[41][84] Mademoiselle magazine also began housing its guest editors at the Barbizon in 1944;[111][112] the program, which mentored 20 interns per year, operated for the next three-and-a-half decades.

[113] Bren wrote that the Barbizon's women-only policy allowed Mademoiselle's editors the "freedom to come to New York and get a head start on their own lives as career women".

[121][122] The commission asked the Barbizon to start accepting male residents,[122] but the New York City Council later passed an amendment exempting single-sex residential hotels from the law.

[42] Assistant manager Mae Sibley told The Wall Street Journal that occupancy rates had decreased because young women "haven't any morals anymore".

[124] Workers also renovated the restaurant and coffee shop; repainted various interior spaces; restored the plasterwork and carpeting; and added TVs, washing machines, and dryers.

[44][137] The Barbizon Hotel for Women dropped the last two words in its name and started accepting male guests on February 14, 1981, coinciding with Valentine's Day.

[147] The company hired architect David Kenneth Specter and interior designer Judith Stockman to finish the renovation, which included three restaurants, a ground-level retail arcade, and a health club at the base.

[155] The four men planned to spend at least $10 million on renovating the hotel into a European-inspired "urban spa",[155] which Schrager said would "be a sanctuary, a total atmosphere".

Following the September 11 attacks, when hotels in New York City saw decreased business, Melrose decided to spend $5 million on renovations within 20 months.

[80] Melrose allegedly enforced a strict English-only policy among staff members; this prompted several Spanish-speaking employees to sue the hotel in 2004, claiming that they had been fired or forced to resign.

[86] To promote the condominium complex, the developers of Barbizon/63 launched a marketing campaign featuring past residents of the hotel, such as Monegasque princess Grace Kelly.

[77] Male visitors included writer J. D. Salinger, who sat in the building's coffee shop while pretending to be a Canadian hockey player, and actor Malachy McCourt, who claimed to have successfully sneaked into the upper stories.

[18][199] A commentator for Newsday wrote in 1978 that "the lobby is positively chic looking, the restaurant good and modestly priced, and both the swimming pool and upstairs library-lounge bonus delights".

[162] Arthur Kaptainis of the Montreal Gazette wrote that the lobby's "soothing early-Gothic look should lower your blood pressure nicely after a hard afternoon of glitz".