The university relocated from Center City to West Philadelphia in the 1870s, and its oldest buildings date from that period.

Selected properties have been recorded by the Historic American Buildings Survey, as indicated in the table below.

[2] One of them, the Lea Laboratory of Hygiene ("Smith Labs"), was demolished in 1995.

Three contributing properties within the Historic District — College Hall, Furness Library, and Richards Medical Research Laboratories — are separately listed on the NRHP.

St. Anthony Hall House is adjacent to the Historic District, and was listed on the NRHP in 2005.