[2]: 31–2 [4]: 144 The B&PD and its merger successor company, the Philadelphia, Wilmington and Baltimore Railroad (PW&B), transferred passengers to the B&O's first downtown depot at East Pratt and South Charles streets by a horse-drawn car on B&O's connecting track.

[2]: 32  By 1838, the PW&B was carrying passengers from further northeast through Philadelphia to Baltimore, where they could transfer to the B&O and continue west to Ohio or by a new branch line further south to the national capital at Washington, D.C.[5] The PW&B started building its own station at the southwestern corner of President Street with Canton Avenue with train yards, including a roundhouse, shops and freight warehouses of about six square city blocks, extending east along Canton Avenue, later renamed Fleet Street.

[7][8] In addition to the brick head house with a distinctive arched roof, the original station also had a 208 feet (63 m) long barrel vaulted train shed over the tracks.

Both units were heading to Washington to reinforce defenses in response to the requests for troops in his proclamation declaring the existence of an insurrection by President Lincoln after the firing on Fort Sumter in Charleston harbor in South Carolina by newly organized Confederate States military forces a few days earlier.

[17][18] In 1873, the newly organized Union Railroad built a new set of tracks in northeastern Baltimore, connecting the original PW&B main line with the Northern Central Railway (NCRY) going north to York and Harrisburg, Pennsylvania.

[9] In 1979, the derelict building was acquired by the City of Baltimore, which planned to demolish it to clear the way for a proposed southern extension of the Jones Falls Expressway (Interstate 83).

[7] In 2009, the City of Baltimore announced plans to designate the old depot as a landmark, which would restrict modifications to the building's exterior, and to request proposals for commercial development of the grounds.

[25] The director of Baltimore City's Commission for Historical and Architectural Preservation, which will review proposals, said that any commercial use "must be subordinate to the history" and that a multi-use partnership would be ideal.