Berwick was first inhabited by American Indians along the Susquehanna River.  In 1786, Evan Owen, an Englishman, decided to settle on the land which is now called Berwick.  He had originally purchased land from William Penn in the areas from around Bloomsburg all the way to Berwick.  He decided to sell his land in Bloomsburg, however, he settled in Berwick.  He wanted to settle a village opposite the mouth of the Nescopeck Creek.  So, in 1780, he began to plot out and survey lots here.  Six years later, he coaxed the first settlers to move here.  Englishmen John and Robert Brown became the first settlers in Berwick in 1786.  They called the settlement "Owensburg", however, Owen, a humble Quaker, renamed the land "Berwick".  He named it this because the wife of one of the Brown brothers hailed from Berwick-Upon-Tweed, Northumberland County, England.  Owen continued to sell lots to people, in particular, many settlers from the Philadelphia area.  Early settlers had the bare essentials; therefore, the community shared many things, such as farmed land and wild game.

Evan Owen built a road over a two year period to connect Berwick to Lehigh.  This was an expansion of a Native American trail that had already been built.  It was now wide enough to fit vehicles through.  In an effort to build better and easier transportation, the state legislature funded a bridge to connect Berwick to Nescopeck, across the Susquehanna River.  The bridge was built in 1807 and took 7 years to complete.  It cost $52,000.  It was 1260 feet long and rested on heavy planked timber.  The original bridge was destroyed in 1835 by an ice flood in the river.  The bridge was rebuilt.
Because Berwick was located along the heavily traveled Susquehanna River, there was a great potential for growth and expansion, especially in the area of industry.  The many stage coaches that traveled through the area created an early need for hotels.  Included in these hotels were the Berwick Hotel, Hotel Morton, and St. Charles Hotel, where St. Charles Park sits in the downtown today.  Improvements to highways and the canal, which was built in Berwick in 1831, made growth possible.  In 1858, the canal was sold to the railroad company, which was a clear sign that industry was on the move.  The earliest industries in Berwick included coopers, carpenters, blacksmiths and other specialties, chair makers, gunsmiths, weavers, dyers, masons, cabinet makers, pottery, butchers, and others.