Drawn to the area by abundant fish and game, the Lenni Lenape Indians, commonly called the Delawares, are believed to be the original inhabitants. During their time in the area, they gave name to many waterways, two of which make up our border, the Quittapahilla and Swatara Creeks. Later the land was inhabited by Scotch-Irish "squatters" in 1650 and Germans followed shortly after to farm the rich soil they found so familiar.

The town of Palmyra, originally Palmstown until 1810, was founded by a Revolutionary War physician and soldier, Dr. John Palm, ten years after he secured a 100-acre tract from Conrad Raish in 1766 (originally surveyed in 1751 for Johannes Deininger). His home stood at about the center of the 100 block of West Main Street. The footprint of the town at that time can be traced along the east side of North Railroad Street, south to West Maple Street, and west onto the Dauphin County line. It became well known as a horse stop; a place to eat, drink, and be merry, as major routes of land, water and rail travel developed through the area. Horseshoe Pike - Route 322 - was used by farmers to barter their grain and produce for merchandise from the town's shopkeepers.

In the midst of establishing the town of Palmyra, Londonderry Township developed under a petition of residents from Derry Township, Lancaster County in 1768.

Finally, in 1894, Londonderry was divided into North and South Londonderry Townships.

The production of shoes (1890) and bologna (1902) found their home in Palmyra. Seltzer's Bologna operates and remains a local landmark to this day. By November 13, 1913 the Borough was established shortly after Milton S. Hershey's new chocolate factory brought great stimulus to the town.