The Baltimore and Ohio Railroad began America's first railroad here in 1829. The first regular passenger service started on May 22, 1830, when a horse-drawn train traveled 13 miles to Ellicott Mills, now Ellicott City.
On May 24, 1844, Samuel Morse's telegraph carried the first message, "What hath God wrought?", from Washington, D.C. to this site. The museum opened in 1953 and now has the largest collection of 19th-century locomotives in the country.
The station and the museum were named a National Historic Landmark in 1961. In 2021, the National Park Service added the Mount Clare Station building to its Underground Railroad Network to Freedom, because freedom seekers used the B&O Railroad on their journeys.

