[3] It is the principal city of the Lewistown, PA Micropolitan Statistical Area, which encompasses all of Mifflin County.

The borough was incorporated in 1795 and was named for William "Bill" Lewis, a Quaker and a member of the state legislature.

Early roads crisscrossed the region, but it was the construction of the Pennsylvania Canal and the railroads that followed that gave stimulus to Mifflin County as an economic force in the state.

Lewistown, as the major city in Mifflin County, saw its economy expand dramatically as entrepreneurs launched companies to construct canal boats or build inns offering lodging for travelers and workers.

But with the demise of the canal system, Mifflin County eventually lost its place as a major transportation hub.

On April 16, 1861, as the American Civil War broke out, Lewistown sent its Logan Guards, a militia group formed in 1858, to defend the national capital of Washington, D.C.

Monument Square, situated at the intersection of Main and Market Streets in Lewistown, serves as a memorial to these men.

Rainfall from the storm over the Mid-Atlantic region ranged from 2 to 3 inches (51 to 76 mm) in the extreme upper basins of the Potomac and North Branch Susquehanna Rivers to 18 inches (460 mm) near Shamokin, Pennsylvania, in the Main Stem Susquehanna River basin.

The facility, located on the banks of the Juniata River across from Lewistown proper, manufactured rayon fiber (primarily for rayon-belted automobile tires), polyester, and Avistrap.

Rayon production, and with it, thousands of good-paying jobs, moved to another FMC plant in Front Royal, Virginia.

First Quality, an adult incontinence products manufacturer, opened a facility in Lewistown that employs approximately 400 people.

The construction of an enhanced highway system between Lewistown and State College was completed in 2020 and better connects the two communities.

The source of the borough's city water comes from the Laurel Creek Reservoir, which is located in Seven Mountains going towards State College.

It is also home to the only local Catholic Elementary school, Sacred Heart of Jesus [1], which educates children of any religion in grades K–5.