In order to ensure peaceful coexistence with the Indians residing in this region, Penn purchased the land with wampum and other valuable commodities including items of clothing, fish hooks, axes, knives and other useful tools.

The area between the Pennypack and Neshaminy Creeks, encompassing Southampton Township, was conveyed by the Lenni-Lenape Chief Tamanend to William Penn by Deed dated June 23, 1683.

In the mid-19th century the villages of Davisville, Churchville, and Southamptonville (formerly "Fetter's Corner") sprouted at the various crossroads in the township, and Second Street Pike became a toll road.

In 1785 inventor John Fitch was living in Warminster and tested a 23" model of a steamboat in a small stream on his friend Joseph Longstreth’s property, behind the current General Davis House on Street Road, on the western end of what is now Upper Southampton Township.

Electricity and telephone lines were installed, and Street Road has been widened (1969–1970) and a railroad overpass constructed, necessitating the removal and/or demolition of the toll house, several shops and residences.

Southamptonville's former one-room schoolhouse has been enlarged to such an extent that it is no longer recognizable as such, but stands in its original location on the south side of Street Road near the railroad overpass.

Upper Southampton Township has embraced industry and development, but retains a certain small-town feeling despite rapid growth in the post-war years, and again in the 1980s and 1990s.