Like all of Manhattan's major north-south Avenues, First Avenue was proposed as part of the Commissioners' Plan of 1811 for Manhattan, which designated 12 broad north-south Avenues running the length of the island. The southern portions of the Avenue were cut and laid out shortly after the plan was adopted. The northern sections of the Avenue would be graded and cut through at various intervals throughout the 19th Century as the northward development of the island demanded.
Starting in the south, First Avenue passes through the East Village, once a predominantly German then Jewish neighborhood, now a trendy area populated mostly by young professionals. Leaving the East Village First Avenue runs by a succession of large urban development projects that sit on what used to be a working industrial waterfront. Stuyvesant Town and Peter Cooper Village, two middle income housing developments, fill the east side of the avenue from 14th to 23d Streets. A Veterans Affairs hospital, the Bellevue Hospital Center, and NYU Medical Center fill the blocks from there to 34th. Between 42d and 47th, the avenue runs past United Nations Headquarters and is called United Nations Plaza, with four lanes running in the First Avenue Tunnel to divert traffic from the Plaza.
Crossing under the Queensboro Bridge and entering the Upper East Side, First Avenue runs through a number of residential areas of varying character and income, and serves as one of the main shopping streets of the Yorkville neighborhood, historically a German and Hungarian neighborhood, today a mix of upper middle class residents. Much of the housing in this area was built for lower income immigrants in the 19th Century, therefore compared to the rest of the Upper East Side, the older buildings along First Avenue are relatively affordable today (relatively being the key word here). In this area First Avenue is also known as "Bedpan Alley" (a play on "Tin Pan Alley") because of the large number of hospitals located nearby.
Crossing 96th Street, First Avenue runs through Spanish Harlem, a historically Puerto Rican neighborhood. Before Puerto Rican migration in the 1950s, much of this area was populated by Italians and known as "Italian Harlem". First Avenue in Italian Harlem was the site of a major open-air pushcart market in the late 19th and early 20th Centuries. There is still a small Italian enclave in the Pleasant Valley section of East Harlem, between 114th and 120th Streets. The northern reaches of First Avenue, north of roughly 110th Street have also seen a significant increase in Mexican residents.