Through the 19th century, Murray Hill was relatively isolated from the rest of New York City, which at the time was centered in Lower Manhattan.

Today, it contains several cultural institutions such as the Morgan Library & Museum, as well as missions and consulates to the nearby United Nations headquarters.

[4][5] The modern neighborhood was once an abrupt, steep-sided mound of glacial till typical of Manhattan Island's still-unmodified post-glacial terrain.

It was described by one author as a "hill of the rudest and most heterogeneous mixture of stone and gravel and boulders, cemented together into a matrix of almost impenetrable density existed, crowning the underlying schist...

[5] During the 19th century, modern-day Murray Hill was "uptown" with the city ending with the reservoir at Fifth Avenue and 42nd Street covering what today is the New York Public Library Main Branch and Bryant Park.

A stream called t'Oude Wrack (Dutch for "Old Wreck") ran across the area, emptying into Sunfish Pond, located at the present-day Park Avenue South and 31st Street in Kips Bay.

[7] A glue factory polluted Sunfish Pond heavily during the 1820s; it was infilled in 1839 after most of its water was used to extinguish a fire at the New York House of Refuge.

[15] This definition explicitly excludes Tudor City, just north of 40th Street between First and Second Avenues, which the community board's chairman said in 2021 "is considered its own neighborhood".

[16] Additionally, "the younger, more bar-centric area south of the neighborhood in the upper 20s and lower 30s" is sometimes held to be part of Murray Hill.

Summarizing the conflicting boundaries, Muschamp said that a then-recent survey of residents found many were unable to distinguish Murray Hill by its name.

[4][25] Like the other grand projects created by distinguished residents upon Manhattan's prominent rises of ground, the Murray house was used for purposes other than farming.

[c] According to historians Edwin G. Burrows and Mike Wallace, while some of these farms were for-profit enterprises, "their primary purpose—besides providing refuge from epidemics—was to serve as theaters of refinement".

[22] During the American Revolutionary War, Mary Lindley Murray is credited with delaying William Howe and his army during General Washington's retreat from New York following the British landing at Kip's Bay, September 15, 1776.

The most common version of the story is that Mrs. Murray invited the officers to tea[d] and succeeded in delaying the British troops for a period sufficient to allow a successful American retreat.

[45][46] In the winter of 1808 during the embargo that closed New York Harbor, a work relief program kept out-of-work dock workers busy reducing the height of Murray Hill.

[27]In 1833 the railroad cut was begun, to carry the New York and Harlem Rail Road through Murray Hill; the route under the most prominent obstacle in its right-of-way was opened on May 1, 1834.

Instead stylish merchandising was changing the neighborhood; Madison Square Park, at this time considered a part of Murray Hill, was bordered by the fashionable ladies' shops of the day on Fifth Avenue.

Though housing in the neighborhood is slightly cheaper than in fashionable nearby parts of Manhattan, prices for apartments here rose greatly during the boom of the late 1990s and early 2000s—as much as 500 percent in a decade.

The eastern part of Murray Hill, between FDR Drive and First Avenue from 34th to 41st Streets, formerly contained industrial uses including a Coca-Cola bottling plant, Consolidated Edison's Kips Bay Generating Station, the Kips Bay Brewing Company, and Con Edison's Waterside power plant.

In the 1980s some of these blocks were rezoned to allow for residential development, which led to the construction of the Rivergate, Manhattan Place, and Horizon high-rise apartment buildings.

[57] The billionaire developer Sheldon Solow purchased the blocks between 38th and 41st Streets in 2000 and demolished the sites in anticipation of the construction of a multi-building complex.

[2] In 2018, an estimated 10% of Murray Hill and Stuyvesant Town residents lived in poverty, compared to 14% in all of Manhattan and 20% in all of New York City.

Based on this calculation, as of 2018[update], Murray Hill and Stuyvesant Town are considered to be high-income relative to the rest of the city and not gentrifying.

[68] The Whitney Museum of American Art opened a branch gallery at the Philip Morris headquarters opposite Grand Central Terminal in April 1983;[69] it closed in January 2008, after 25 years.

[84] For more than 60 years, the offices of William F. Buckley Jr.'s journal of opinion, National Review, were located in the neighborhood, at 150 East 35th Street and then at 215 Lexington Avenue.

[64]: 14 The concentration of fine particulate matter, the deadliest type of air pollutant, in Murray Hill and Stuyvesant Town is 0.0102 milligrams per cubic metre (1.02×10−8 oz/cu ft), more than the city average.

[64]: 6  The percentage of Murray Hill and Stuyvesant Town students excelling in math rose from 61% in 2000 to 80% in 2011, and reading achievement increased from 66% to 68% during the same time period.

[112] Murray Hill and Stuyvesant Town's rate of elementary school student absenteeism is lower than the rest of New York City.

[65]: 24 (PDF p. 55) [64]: 6  Additionally, 91% of high school students in Murray Hill and Stuyvesant Town graduate on time, more than the citywide average of 75%.

Nevertheless, the name MUrray Hill is still applicable, as many East Side phone numbers in area code 212 still begin with 68, which corresponds to MU on the telephone keypad.