Designed by New York City architect Kenneth MacKenzie Murchison (1872–1938), it was constructed in 1911 in the Beaux-Arts style of architecture for the Pennsylvania Railroad.

[7] The building sits on a raised "island" of sorts between two open trenches, one for the Jones Falls Expressway and the other for the tracks of the Northeast Corridor (NEC).

The Savarin Restaurant, located at the west end of Baltimore's station, was originally decorated with Chesapeake Bay-themed murals and had an entrance and exterior signage directly fronting Charles Street.

[10] In 2004, Baltimore, through its public arts program, commissioned sculptor Jonathan Borofsky to create a sculpture as the centerpiece of a re-designed plaza in front of Penn Station.

His work, a 51-foot (15.5 m)-tall aluminum statue, named Male/Female, has generated considerable controversy ever since, with The Baltimore Sun reporting what it called a "maelstrom of criticism".

[11] Its defenders cite the contemporary imagery and artistic expression as complementing an urban landscape, while opponents criticize what they decry as a clash with the station's Beaux-Arts architecture and detracting from its classic lines.

[19] In April 2019, it was announced that development would encompass a transit-oriented hub of apartments, shops, offices, a hotel, and redevelopment of nearby property owned by the passenger railroad.

[20] Amtrak describes the plan as creating a premier regional transportation hub to accommodate passenger growth as the next generation of high-speed Acela Express trains start running along the Northeast Corridor in 2021.

[21][22] In a June 8, 2021, editorial, The Baltimore Sun reported that the controversial male/female aluminum statue is not shown in the development team's conceptual drawings for the station plaza.

Until the late 1960s, the PRR also operated long-distance trains over its historic Northern Central Railway line from Penn Station to Harrisburg and beyond, such as "The General" to Chicago, the "Spirit of St. Louis" to its Missouri namesake, and the "Buffalo Day Express" and overnight "Northern Express" between Washington, DC, and Buffalo, New York.

Baltimore Penn Station is also used for MARC train storage during the weekends and overnight via off-peak service times on tracks 2, 3, 5, and 8.

Penn Station offers a magazine store that sells quick necessities, and two restaurants: Dunkin' Donuts and Java Moon Cafe.