Its founder, David G. Seixas (1788–1864), was a Philadelphia crockery maker-dealer who became concerned with the plight of impoverished deaf children who he observed on the city's streets.

More space became needed to accommodate additional children as Seixas' humanitarian efforts became known, so he rented an office at the southeast corner of Eleventh and High (later Market) Streets to serve as a school.

The organization was chartered by the Commonwealth of Pennsylvania as "an asylum and school in the city of Philadelphia, where the children of the rich, for a moderate compensation, and of the poor, gratuitously, laboring under the privation of the faculty of speech, are maintained and educated."

Completed in 1826 and later incorporating two additions, this building is an excellent example of major works by three of America's most important 19th-century architects: John Haviland, William Strickland and Frank Furness.

Under the title Pennsylvania Institution for the Deaf and Dumb, the former campus at 7500 Germantown Avenue was added to the National Register of Historic Places (NRHP) on May 9, 1985.