Before European settlers arrived in the Tulpehocken Creek valley, the area was inhabited by the Lenape. In 1723, thirty-three Palatine families from Schoharie, New York, moved to the confluences of the Tulpehocken and Northkill Creeks. By 1735, a saw and grist mill was located three and a half miles up the Tulpehocken river from Bernville.
In 1737, Stephanus Umbenhauer immigrated from Bern, Switzerland, and purchased 220 acres (0.89 km2) from Thomas Penn. In 1819, Stephanus'''' grandson, Johann Thomas Umbenhauer, set aside 46 acres (190,000 m2) to be divided into 62 lots. On 24 August 1819, Peter Bennethum bought the first six lots. In January 1820, the town was named Bernville after Stephanus'''' birthplace. The first house was built by Philip Filbert in 1820. In 1828, the Union Canal was completed, connecting the Susquehanna and Schuylkill Rivers. Union Canal Lock #36 was located at the southwest corner of Bernville Borough, near where Northkill Creek empties into Tulpehocken Creek. An historic marker on Route 183 states: "The canal, at this point, followed the north bank of the Tulpehocken. A dam, two locks, and a mule bridge made it possible for boats to cross Northkill Creek. Nearby were grist mills, a lime kiln, and a tannery." Due to the proximity of the Bernville Locks and the town''''s location on the canal, Bernville was a primary and prospering canal port.
In 1851, the village of Bernville, discontent with Penn Township?s road maintenance and community services, incorporated as a borough. The borough included the original 62 lots, most of which measured 60'''' x 260''''. In 1884, the Union Canal closed. With no canal or railroad access, Bernville withered. In 1950, Bernville Borough annexed property from Penn Township at both ends of Main Street.
Stanton H. Clay, who died in December 2004, was mayor of Bernville for 45 years, from 1951 to 1996.