In 1829 Eastern State Penitentiary opened on Fairmont Ave between 21st and 22nd Streets in Philadelphia, Pennsylvania. It radial floor plan of prison wings growing from a center room, like spokes on a wheel, inspired the design of more than 300 other prisons worldwide. Eastern State is credited for creating the "Pennsylvania System" of prison direction, based on solitary confinement. The prisoner was supposed to go through spiritual reflection and change his was of life due to being isolated and therefore left to his own thoughts and devices. Inmates were hooded when outside his cell, and no contact with other prisoners was tolerated.

Prisoners sat in small windowless rooms with running water and a toilet, which was considered state of the art because most buildings of the time did not possess such creature comforts. Thick soundproof walls and personal exercise yards prevented almost all contact with others. Doorways were intentionally short, because the prisoner was supposed to stoop down in order to feel humility, and the only lighting in the entire room was a very small and narrow window in the ceiling, referred to as "The Eye of God." Books and reading material were not permitted, as the prisoner was supposed to reflect on his wrongdoing. Many inmates housed at Eastern State ended up going insane due to the isolated conditions. In fact, so many cases of insanity were reported, doctors started creating other reasons for such outbreaks of mental illness, such as masturbation.

Solitary confinement came to an end in the 1870s, mostly due to budgetary constraints. Most of the cells were renovated between 1900 and 1908, and suddenly a room that once housed one man was home to as many as 5. The prison population swelled to 1700 in 1913.

On April 3, 1945, a major prison escape was carried out by twelve inmates (including the infamous Willie Sutton) who dug a 97-foot tunnel under the prison wall to freedom. After the tunnel was finished, the inmates snuck out at varying times to avoid being noticed missing and the last two were caught climbing out of the tunnel. The others were caught a few blocks away.

The 1960s brought rampant rumors of a closing. The building was falling apart and overcrowded. Costs to renovate were placed as high as simply building a new prison.  Eastern State eventually closed in 1971. The city of Philadelphia purchased the property with intentions to redevelop, but the site was designated a National Historic Landmark in the mid-1970s. Now the prison is a tourist attraction kept in "preserved ruin," meaning it has been kept in its dilapidated state without restoration. Tours are given to the public from April 1 to November 30.

Because of its unusual features, the prison has been the site of many television shows and movies. The Sci Fi Channel shot an episode of Ghost Hunters and MTV also shot Fear in the building, and the movie Twelve Monkeys shot mental hospital scenes in its halls.