Carlisle is a borough in and the county seat of Cumberland County, Pennsylvania, United States. The name is traditionally pronounced with emphasis on the second syllable. Carlisle is located within the Cumberland Valley, a highly productive agricultural region. As of the 2000 census, the borough population was 17,970. Carlisle is the smaller principal city of the Harrisburg–Carlisle Metropolitan Statistical Area, which includes all of Cumberland, Dauphin, and Perry counties in South Central Pennsylvania. Carlisle is located at 40° 12' 09"N 77° 11' 42"W at an elevation of 479 feet above sea level. The borough lies in the Cumberland Valley, a section of the Great Appalachian Valley, on the south side of Conodoguinet Creek, a tributary of the Susquehanna River. Letort Spring Run, a tributary of Conodoguinet Creek, runs north through the eastern part of the borough.

Carlisle lies in south-central Pennsylvania at the intersection of Interstate 76 and Interstate 81 roughly 20 miles west-southwest of Harrisburg, the state capital. It is approximately 69 miles northwest of Baltimore and 108 miles west-northwest of Philadelphia. According to the United States Census Bureau, Carlisle has a total area of 5.4 square miles, all of it land.

Carlisle was laid out and settled by Scots-Irish immigrants in 1751 and became the center of their settlement in the Cumberland Valley. It was named after its sister town of Carlisle, England, and even built its former jailhouse (still standing and in use by Cumberland County as general government offices) to resemble Carlisle Citadel. Carlisle was initially part of Lancaster County. Carlisle was incorporated as a borough on April 13, 1782. As authorized by a general borough law of 1851 (amended in 1852), the government is administered by a burgess and a borough council.

In 1787 Carlisle was the scene of a riot instigated by Anti-Federalists in response to a planned march in favor of the US constitution. In 1794 during the Whiskey Rebellion, the troops of Pennsylvania and New Jersey assembled in Carlisle under the leadership of George Washington. On a related note, George Washington worshipped during that time in the First Presbyterian Church at the corner of Hanover and High streets. The borough was shelled by the Confederates on July 1, 1863, during the Battle of Carlisle, part of the Gettysburg Campaign of the American Civil War. On a column in front of the city's historic courthouse, evidence of the cannonballs' destruction can still be seen. Carlisle was well-known at one time for the Carlisle Indian Industrial School, which trained Native Americans from all over the United States; one of its notable graduates was athletic hero Jim Thorpe. However, some view the Carlisle School as the first of many schools that were used for "cultural genocide" of American Indians.

Carlisle is also home to Dickinson College, established in 1773 and later chartered in 1783, making it the first college founded in the newly recognized United States. The Dickinson School of Law, founded in 1834 and affiliated with Dickinson College until 1914, is the fifth-oldest law school in the United States and the oldest law school in Pennsylvania. It remained independent for over 80 years, until it merged with Pennsylvania State University in 1997, becoming the Penn State Dickinson School of Law.

The U.S. Army War College, located at the Carlisle Barracks, caters to high-level military personnel and civilians and prepares them for strategic leadership responsibilities. The Carlisle Barracks is the oldest installation in the United States Army and the Army's most senior military educational institution. Carlisle is home of the U.S. Army Military Heritage Museum.