Before Franklin County was created, Southampton Township was established originally from portions of Lurgan and Hopewell Townships in October, 1783.  It was created upon the complaints of settlers, who argued that the existing townships, Hopewell and Lurgan, were too long, extending “from the North to South Mountains at a distance of about fifteen miles.”  As a result Southampton Township was created from the southern portions of Hopewell and Lurgan Townships. The next year in September, 1784, Franklin County was formed out of Cumberland County and divided Southampton Township into two parts.  Each part established its own political subdivision creating two Southampton Townships, one in each county.

Three villages were established in the Cumberland County section of Southampton Township.  Middle Spring, about two miles north of Shippensburg, was the site of a Presbyterian meeting house in 1737.  It is named for the spring and the old church that are located there.  Leesburg was populated four miles east of Shippensburg by Scots-Irish families.  The town was named for George Lee, who ran a tavern in a log house which stood on the south side of what is now Walnut Bottom Road.  Cleversburg was formed around 1860 just south of the center of the Township, about one mile from South Mountain.  It was named in honor of George Clever, upon whose lands it was established.

Michaux State Forest is located in the southern portion of the Township.  It is administered by the Pa. Department of Conservation and Natural Resources and was named in honor of Andre Michaux, a French botanist, dispatched by the King and Queen of France in 1785 to gather plants for the Royal Gardens. He discovered and named many flowers, shrubs and trees previously unknown in the newly independent United States.

The creation of Michaux State Forest was a direct result of the depletion of the forests of Pennsylvania that took place during the mid-to-late 19th century.   In 1897, Pennsylvania passed legislation that authorized the purchase of forest lands, which was the beginning of the State Forest system.  Michaux State Forest was established in 1902.  The Appalachian Trail also traverses the Southampton Township through Michaux State Forest.  The Trail was completed in 1937 and is the longest marked footpath in the United States.

Interstate 81 crosses through the center of Southampton Township and is a major transportation facility on the east coast.  The construction of the Interstate in the western part of Cumberland County, including Southampton Township, occurred in 1962.  The highway in the eastern part of the County, from Carlisle to Harrisburg, was completed in 1975.