It is served by the Lake Shore Limited route, which provides daily passenger service between Chicago and (via two sections east of Albany) New York City or Boston; Erie is the train's only stop in Pennsylvania.

The entire exterior is clad in "rough brown" brick and sandstone layered in a Flemish bond, trimmed in terracotta, and lined with granite at the ground level.

The concourse, off the rotunda, led to the Peach Street entrances, and contained space for a soda fountain, a barber shop, and telegraph offices, as well as access to the station's 111-by-35-foot (34 m × 11 m) waiting room.

[8][9] The entire ground floor was laid with terrazzo featuring a mosaic border and Botticino marble paneling along the plaster walls.

[9] The station's low-level, concrete platforms are approximately 450 feet (137 m) long covered by steel, "butterfly-style" canopies with wooden roof decking.

A bomb shelter, still stocked with cases of "U.S. Civil Defense All-Purpose Survival Crackers" from the early 1960s, is next to the station's boiler room and its three coal-fed furnaces.

[19] Construction on a new station was started in early 1865 as a joint venture between the Cleveland, Painesville and Ashtabula and the Buffalo and Erie railroads, and was completed in February 1866.

[15] In addition to the leased space, the Philadelphia and Erie continued to maintain a freight station on State Street below Hamot Hospital for several years afterward.

[14] The station, known as Union Depot, consisted of a brick Romanesque Revival structure facing Peach Street between two sets of railroad tracks.

[20] The depot was equipped with the modern amenities of the day including outdoor gas lighting, a barber shop, gentleman's and ladies' parlors, and a dining room; the second floor contained offices and sleeping quarters for railroad officials.

[21] The Cleveland, Painesville and Ashtabula became the Lake Shore and Michigan Southern Railway in 1869, and absorbed the Buffalo and Erie Railroad later that year.

[28] The committee felt it was desirable that, on account of Erie's topography and the existing railroad grades, the tracks be raised in the downtown to accommodate new roadway underpasses.

[29] The work to re-grade and install drainage on Peach and Sassafras Streets coincided with the building of the station from 1925 to 1927, and cost the city approximately $110,000 (equivalent to $1.93 million in 2023).

[33] In the 1930s, the New York Central provided the majority of the service in Erie with over 20 trains daily, including the original Lake Shore Limited and the New England States.

[36] The Bliley Electric Company, a manufacturer of crystal oscillators used in radio transmitters and receivers, moved from 8th and Peach Streets to space on the second floor of Union Station in 1933.

[39] The post-war boom in automobile travel and the construction of the Interstate Highway System, as well as competition from commercial airlines, led to the decline of passenger rail.

[45] Amtrak continued to operate a New York-to-Chicago train until January 1972, the Lake Shore, which had a station stop in Erie starting in November 1971.

[46][47] Erie remained devoid of any passenger rail service until Amtrak reintroduced the former New York Central train, the Lake Shore Limited, on November 30, 1975.

[33][41][49] At one point, in 1973, the Pennsylvania Department of Labor and Industry ordered Penn Central to close Union Station citing "sanitary reasons"; at the time, it was only used by the crews of its freight trains.

[49][51] The few passengers that did travel by train were often reluctant to use Amtrak's makeshift waiting room in the station rotunda, due to the unsettling sights and fear of being accosted.

When Hoppers relocated and became a full production brewery under the name of Erie Brewing Company, Porters, a fine dining restaurant and beer bar, opened in its place.

[58] During the run-up to the 2008 presidential election, Union Station was site of a "whistle-stop" by ABC's Good Morning America news team on a charter Amtrak train.

Sam Champion, Chris Cuomo, Robin Roberts, and Diane Sawyer, the news anchors, interviewed local residents at the Brewerie about campaign issues.

[64] Union Station is on the Lake Shore Subdivision, the CSX Transportation main line from Erie to Buffalo, New York, at railroad milepost 86.9.

[2] The rest of the building is leased out to a variety of tenants including Amtrak, the Brewerie, a hookah lounge, a wine shop, a hair salon, a banquet hall, and an art studio.