The interior includes a series of 13 murals created by Ben Shahn and Bernarda Bryson for the U.S. Treasury Department's Section of Fine Arts.

[7] Hostos Community College and the entrances to the New York City Subway's 149th Street–Grand Concourse station are directly to the south, while Lincoln Hospital is to the southeast.

[4][18] There is a band course running across the facade above the Grand Concourse entrance, which bears the inscription "Bronx – United States Post Office – New York".

[19][20] Rudy's sculpture depicts a dove giving a message to the biblical figure Noah after a great flood,[19] an allusion to the USPS's unofficial motto "Neither snow nor rain nor heat nor gloom of night stays these couriers from the swift completion of their appointed rounds".

[ii][46] The New York Times wrote that the construction of the post office building would help spur development along 149th Street,[47] which was located near the Mott Avenue subway station and several businesses.

[6][48] The federal government subsequently moved to acquire the rest of the block, extending west to Mott Avenue (now the Grand Concourse), by eminent domain.

[51][52] The final portion of the allocation was secured in September 1913,[51] and the U.S. government bought 13 buildings at 554–582 Mott Avenue that November, thereby obtaining full ownership of the block.

[43] A $750,000 congressional appropriation for a new post office was proposed in 1916 as part of a wider-ranging bill, which called for $35 million worth of improvements to federal buildings.

[56] Another such attempt occurred in 1919, when $1 million[vii] for a central post office in the Bronx was proposed in the U.S. House's Public Buildings Appropriation Bill.

[53] The Board of Trade called on U.S. Postmaster General Harry New to begin constructing the post office building, an idea that New supported.

[60] In 1929, the Board of Trade and the Bronx Chamber of Commerce again requested that a central post office be constructed at Mott Avenue and 149th Street.

[70] Postmaster General James A. Farley said in February 1934 that the Post Office Department was considering a "concentration and distribution" building at the Grand Concourse and 149th Street.

[x][76] This funding was made available through the Public Works Administration (PWA) program, which also included the development of 28 other buildings in New York City and several thousand more such projects nationwide.

[76] The post office was to have a garage in the rear and employee rooms on the second story, and it would be sturdy enough to support the future construction of additional floors.

[85] Construction was halted temporarily in September 1936 after stonecutters on the site went on strike, alleging that non-union laborers had been employed to cut the Vermont marble;[85][86] at the time, the building had been erected to the first floor.

[93] Shortly after the Bronx Central Annex's completion, the Treasury asked artists to submit designs for 13 murals that were being planned for the building's lobby; the winner was to receive $7,000.

[100] An automatic mail-sorting machine known as the Mailomat was installed at the Bronx Central Annex in 1947, allowing patrons to send mail when the building was closed.

[104] In addition, to encourage patrons and mail carriers to have themselves tested for tuberculosis, the New York City Department of Health temporarily installed an X-ray machine in the building's lobby in 1955.

[108] The United States Congress received plans in July 1963 for $2.3 million[xv] in modifications to the Bronx General Post Office, which was to be renovated after other federal agencies had moved out of the building.

[13] However, two other city agencies asked the LPC to defer the designation, as the Post Office Department's successor, the United States Postal Service (USPS), was considering expanding the building.

[16] The building's manager, Anthony Kienle, conversely said that graduate students visited the post office to write dissertations about the murals.

[126][127] By the mid-1990s, the Bronx General Post Office was near capacity; the USPS was unable to install new sorting equipment because of a lack of space, and the agency also could not easily expand the building because it was a protected landmark.

[134][135] At the time, the USPS was conducting a feasibility study on whether to consolidate mail-processing facilities, though it denied that such a change would delay mail deliveries in the Bronx.

[135] After U.S. Representative José E. Serrano raised concerns, the USPS Inspector General's office agreed to reconsider plans to relocate the building's mail-processing facility.

[149] Serrano proposed a clause in the congressional spending bill, which would prevent historic post office buildings from being sold until they were reviewed.

Local elected officials favored the proposal submitted by one bidder, Youngwoo & Associates,[143][144] who had suggested turning the building into a marketplace or shopping center.

[159] Youngwoo & Associates and its development partner Bristol Group hired Hollister Construction Services to renovate the Bronx General Post Office.

[164] According to the urban planner Sam Goodman, the area's low median household income and the presence of the Bronx Terminal Market mall nearby meant that there was not much demand for the redevelopment to begin with.

[161] MHP Real Estate Services and Banyan Street Capital tentatively agreed to purchase the General Post Office Building in January 2019 for more than $70 million,[162][165] but the sale was canceled that July.

When the structure was completed, Architectural Forum wrote that the building had successfully combined "a distinct modern influence and the continuing tradition of 'government classic'".