Developed at the intersection of Indian trails along Letort Creek, in the eighteenth century the town of Carlisle became the jumping-off point for traders and settlers heading over the Alleghenies on their way west.

A brief 1756 encampment at Carlisle preceded the more permanent settlement that started in May 1757, during the French and Indian War on the North American front between the colonies of Britain and France.

After the American Revolutionary War, from 1783 to 1837, the town of Carlisle was significant as the frontier gateway, as a greatly increased wave of land-hungry migrants moved west.

While the facility might have been used to store ammunition and explosives, its lack of access to water transportation made it impractical because of the difficulty of overland travel at the time.

[4] In 1794, Carlisle Barracks became the center of intense federal military activity with the outbreak of the Whiskey Rebellion in the Pennsylvania backcountry.

The crisis was posed by farmers in southwestern Pennsylvania, who refused to pay a tax on the commercial whiskey they distilled from their corn crops.

Captain E. V. Sumner found most of the barracks buildings in disrepair, the maneuver area less than adequate, and horses in short supply.

Overcoming these problems included drilling his recruits at the double time on foot to simulate the trotting of the missing horses.

In 1839, Captain Samuel Ringgold arrived to begin training recruits and testing equipment for the "flying artillery," as it was sometimes called.

In spite of a small defensive Pennsylvania militia and home guard force, Brigadier General Albert G. Jenkins' Confederate cavalry entered Carlisle on 27 June.

During and at the end of the Indian Wars, the US government sought a way to assimilate and integrate the children into European-American culture: teaching them English, trades, and Christianity.

[7] The Indian Bureau sent the children to the school to be educated and essentially kept as political hostages, to ensure compliant behavior on the part of the bands from which they had been taken.

[7] Commanding General of the Army William T. Sherman had acceded to the petitions of Richard Henry Pratt to use the barracks for a model Indian school.

Twenty young Indian men gained further education at Hampton Institute, a historically black college, and private schools in New York.

For two years, the hospital provided medical treatment, mental reconditioning and vocational training for more than 4,000 afflicted soldiers returned from service with the American Expeditionary Forces in France.

They applied classroom instruction and field exercises to train in care of casualties and disease prevention, the latter a major problem for the military until improvements in sanitation and antibiotics.

When the Medical Field Service School departed in 1946 for Fort Sam Houston at San Antonio, Texas after World War II, educational innovation continued.

Classes were suspended in 1940 during the preparedness mobilization for World War II, and not resumed until a decade later at Fort Leavenworth, Kansas, for the 1950–51 academic year.

In 2006, ground was broken on a major project across the road from Carlisle Barracks: to construct new military housing, work that had been postponed pending BRAC review.