The mainline route of the Erie Railroad proved influential in the development and economic growth of the Southern Tier of New York state, including the cities of Binghamton, Elmira, and Hornell.

When the route was completed in May, 1851, President Millard Fillmore and several members of his cabinet, including Secretary of State Daniel Webster, made a special, two-day excursion run to open the railway.

It is reported that Webster viewed the entire run from a rocking chair attached to a flatcar, with a steamer rug and jug of high-quality Medford rum.

In fact, current owner Central New York Railroad spent $3.2 million in 2021 centering its single remaining track, re-ballasting and repairing masonry.

As stated in the introduction, the shops in Hornell, New York were the largest on the Erie system beginning in the late 1920s, processing about 350 locomotives per year with "classified" (heavy) repairs.

[4] In August 1859, the company went into receivership due to inability to make payments on the debts incurred for the large costs of building, and, on June 25, 1861, it was reorganized as the Erie Railway.

In the Erie War of the 1860s, four well-known financiers struggled for control of the company; Cornelius Vanderbilt versus Daniel Drew, James Fisk and Jay Gould.

Gould ultimately triumphed in this struggle, but was forced to relinquish control in 1872–73 due to unfavorable public opinion following his involvement in the 1869 gold-rigging scandal and to his loss of $1 million of Erie Railroad stock to the British con-man Lord Gordon-Gordon.

Investors in the railroad were also weary of Gould's financial wars with Vanderbilt that caused wild stock price fluctuations and operating losses from rate battles.

[8] Beginning in 1871, the railroad interchanged traffic by means of truck exchange, including through passenger and freight connections to St. Louis, Missouri, using a Nutter car hoist in Urbana, Ohio.

During the eastern railroad strike of 1913 Underwood agreed to accept any ruling made by mediators under the Newlands Reclamation Act.

Lee, president of the Brotherhood of Railroad Trainmen, asserted that the only way "to deal with the Erie is through J.P. Morgan & Company, or the banks".

Underwood responded from his home in Wauwatosa, Wisconsin, stating "I am running the Erie Railroad: not George W. Perkins, nor J.P. Morgan, nor anybody else.

"[17] In the mid-1920s, the Van Sweringen brothers of Cleveland, Ohio, assumed control of the Erie, and they installed a new president for the railroad, John Joseph Bernet.

[15][18][19] Bernet only served as the Erie's president from January 1927 to May 1929, but during that time, he initiated a reorganization and cost-cutting program to improve the company's operations and finances.

[21] That same year, the Erie purchased a share of the Niagara Junction Railway, along with the New York Central and the Lehigh Valley.

The Erie's large repair facility in Hornell was closed following Conrail's takeover, and operations were consolidated at the Lackawanna's Scranton facility.A map from 1960 shows that the Erie had some control over the former Cleveland, Columbus, Cincinnati and Indianapolis Railway and the New York Central from Lawrenceville to Newberry Junction, near Williamsport, PA.[39] The Erie Railroad operated a number of named passenger trains, although none were as well-known or successful as others like the Pennsylvania Railroad's Broadway Limited or New York Central Railroad's 20th Century Limited.

[40]: 52–53 The Erie operated an extensive network of commuter routes in northern New Jersey and the lower Hudson Valley of New York.

In addition to its steam and diesel services the Erie also operated an electric commuter rail line to its terminal station in Rochester, New York.