The neighborhood is historically significant due to its association with the development of rail transportation in Maryland.

Additional historical significance comes from the neighborhood's association with ethnic immigration to Baltimore.

During the 1840s and 1850s the area was a center of settlement for Baltimore's German and Irish communities, many of whom immigrated to the United States to work in the rail industry.

Later, from the 1880s to the 1920s, the neighborhood became established as the center of Baltimore's Lithuanian immigrant community.

[1] The district is "located directly north of the Baltimore & Ohio Railroad's Mount Clare yard and shops on W. Pratt Street",[2][4] so apparently does not include the Mt Clare Roundhouse, now the B&O Railroad Museum, i.e. the railway roundhouse which contributes to the district's name.