The building was designed in the modern style by Gordon Bunshaft of Skidmore, Owings & Merrill (SOM), in partnership with the firm of Albert Mayer and Julian Whittlesey.

Manhattan House consists of a central "spine" with five wings each facing north and south, as well as low-rise retail podiums to the west and east.

Throughout the mid- and late 20th century, New York Life operated Manhattan House, renting apartments to largely middle-class tenants; its residents included Bunshaft, clarinetist Benny Goodman, and actress and later Princess of Monaco Grace Kelly.

O'Connor ultimately completed the project by himself at a cost of $1.1 billion, making it one of the most expensive condominium conversions in New York City; the last condos were sold in 2015.

[16] New York Life also hired Fellheimer & Wagner to design a two-story structure on the east side of Second Avenue between 65th and 66th Streets,[17] which contained the Beekman Theatre and two banks.

[13][25][31] The New York City Landmarks Preservation Commission (LPC) described the floor plan as an elongated "H",[25] while Architectural Forum characterized the layout as resembling three connected "+" symbols with a "T" at either end.

[28] At the time of Manhattan House's construction, the 1916 Zoning Resolution mandated the inclusion of setbacks on buildings in New York City based on the height of the adjoining street.

To allow the construction of a taller structure with fewer setbacks, New York Life had donated the northernmost 40 feet of the site to the city government, which widened the adjacent segment of 66th Street.

To the east of the eastern entrance are a stairway and ramp leading to a doctor's office; a storefront facing Second Avenue; and a planting bed with granite-block walls topped by an iron fence.

[33] The exterior of Manhattan House resembles a continuous slab, but each of the building's five sections is physically separated to reduce the amount of space required for hallways.

[60] Manhattan House's lobby also contained glass walls on either side, facing the gardens,[60][61] which could be slid open during periods of warm weather.

[80] The 21st floor contains a 7,597 sq ft (705.8 m2) penthouse with nine bedrooms, eight-and-a-half bathrooms, a fireplace, a media room, a private gym, a playroom, and a dedicated service entrance.

[83] The New York Life Insurance Company bought the 66th Street site for $1.6 million,[ii][12][84] beating out bidders that included a film studio.

[6][5] Mayer & Whittlesley and SOM submitted plans for the development to the New York City Department of Buildings in January 1948,[53] but the project was delayed by disputes over the parking garage,[93] which mayor William O'Dwyer ultimately halted in August 1948.

[94] Later the same month, New York Life announced that it had postponed the planned apartment building indefinitely because of rising construction costs; the company would instead use the site as a 500-space parking lot.

[95][96] New York Life announced in April 1949 that the general contractor, Cauldwell-Wingate Company, would immediately begin constructing the building, which was to be known as Manhattan House.

[7][21] New York Life officials hosted a groundbreaking ceremony for the development on April 6, 1949; at that point, the insurance company had already received over a thousand applications from potential tenants.

[iv][25] Charles E. Lane Jr. was hired as the building's resident manager the following month,[98][99] and workers began pouring the concrete floor slabs that August.

[109] The New York Observer reported that one potential resident during the 1970s, a producer for NBC "recalled wearing white gloves to the interview and answering questions about her parents' background despite having long established her own career—and a years-long wait list".

[122] Existing tenants claimed that O'Connor and Kalikow had refused to renew their leases, had increased their rent significantly, and were harassing them with loud construction noises.

[68] A State Supreme Court judge ruled in January 2008 that existing tenants did not have standing to challenge the condo-conversion plan, which the attorney general's office had already approved.

[133] O'Connor wished to sell the building's retail space for $100 million by March 2008,[134] and the attorney general's office declared the offering plan to be effective in August 2008.

[13][146] The actress Grace Kelly, who became the Princess of Monaco in 1956, was another early tenant, relocating to Manhattan House from the nearby Barbizon Hotel for Women.

[129] The clarinetist Benny Goodman lived in one of Manhattan House's penthouse apartments and reportedly invited Bhumibol Adulyadej, then the king of Thailand, to his home.

[150] The next year, the same magazine wrote that Manhattan House "carries out on a large scale, in a big city, an indoor-outdoor synthesis hitherto found mostly in modern country homes".

"[60] Architectural Forum wrote that Manhattan House was "the biggest, whitest, and most interesting postwar mountain of cliff dwellings for New York City's well-heeled natives".

[154] When the original windows were removed in 1982, Paul Goldberger of The New York Times said: "It is shocking to think of a building erected as recently as 1950 as being in need of official landmark protection, but that surely seems to be the case here.

[61] Matt A. V. Chaban of The New York Times wrote in 2016 that "the midcentury mode was seen in the white brick behemoth of Manhattan House on East 66th Street and its myriad imitators".

[156] Although Manhattan House was widely praised, few developments on the Upper East Side followed its lead, largely because of the dearth of available sites in the neighborhood that occupied an entire block.

[159] Historic Districts Council director Simeon Bankoff said that, although white brick had become an overused material, "Manhattan House is an incredibly important building, and it was really the very best of a bad lot.