[6] From 1903 to 1908, the first buildings were constructed on 633.913 acres (256.535 ha) of Crab Hill in Spring City, Pennsylvania, Chester County on what was referred to as the lower campus.

In 1921, Whitman and Wilson I and II were constructed along with Penn Hall for employee housing; in 1929, the assembly building was complete and functioned as the gymnasium and auditorium.

Administration, Philadelphia, Quaker, Rockwell, Franklin, Nobel, Union, Vincennes, Tinicum, Industry, Penn, Devon, Mayflower, Limerick, Assembly, Storeroom, Laundry, Whitman, Wilson I, Wilson II, Hershey (Rockwell, Nobel, Franklin and Hershey were all demolished in 2020) Pershing, Buchanan, Audubon, Keystone, Capitol, Horizon (Buchanan, Audubon, Keystone, Capital were demolished in 2018) The older buildings, designed by Phillip H. Johnson, were two-storied, and made of red brick, terra cotta, and granite trimmings.

Residents were assigned to mattress-making, shoemaking and repair, grading, farming, laundry, domestic duties, sewing, baking, butchering, painting, and working in the store.

In the Biennial Report to the Legislature submitted by the Board of Trustees, Pennhurst's Chief Physician quoted Henry H. Goddard, a leading eugenicist, as follows: Every feeble-minded person is a potential criminal.

[8] In 1916, the Board of Trustees initiated a plan to construct cottages specifically for women to segregate them from the men, in part to prevent pregnancies.

[citation needed] In 1968, conditions at Pennhurst were exposed in a five-part television news report anchored by local WCAU-TV correspondent Bill Baldini.

In 1977, U.S. District Judge Raymond J. Broderick ruled that the conditions at Pennhurst State School violated patients' constitutional rights.

[17] Terri Lee Halderman had been a resident of Pennhurst, and following multiple episodes of abuse, she and her family filed suit in the federal district court.

[19][20] The rulings collectively lent credence to the nascent "deinstitutionalization" movement, which sought to move mental patients from hospitals to halfway houses or reintegrate them into their families.

[11] The rulings also aligned with the increasing tendency of federal courts to take control of school districts, prisons and other state institutions in order to enforce citizens' rights.

[21] As noted below, the institution was eventually closed pursuant to a settlement agreement that required that community-based services be offered to all of its residents.

In 1990, renovations began on Horizon Hall, one of the newest buildings at Pennhurst, as part of a project to establish a nursing facility at the veterans' center.

[citation needed] In partnership with the Preservation Alliance for Greater Philadelphia, PMPA obtained a grant to complete a re-use design and feasibility study of the Pennhurst campus.

[24][25] Penn Organic Recycling LLC operated on 4.5-acre (1.8 ha) of Pennhurst, offering topping, composting and food waste services.

[citation needed] The Travel Channel's television show Destination Fear filmed at the location for the fifth episode of their first season in 2019 .

[citation needed] On June 8, 2021 heavy metal band Motionless in White performed their Deadstream 2: Live at Pennhurst concert on the grounds in front of the main building entrance.