John Canon bought this land from the state of Virginia and established a sawmill and a gristmill along Chartiers Creek in the 1770s. Ten years later, he laid out lots on the land, and his name became permanently attached to it. Since that time, there has been a Presbyterian presence in the region, as evidenced in the establishment by John McMillan of Jefferson Academy (later College) in 1780 in the small log building now at 25 E. College Street. In 1865, Jefferson College merged with Washington College, and four years later all college activities moved ten miles south to Washington ( WS4). The strong denominational presence is also apparent in the brick Canonsburg United Presbyterian Church (1870; 112 W. Pike Street) that has evolved from four separate Presbyterian churches within blocks of one another. The church's massing, ebullient corbeling, and bracket-lined cornice are reminiscent of several other United Presbyterian churches in Washington County, including Westminster United Presbyterian in Burgettstown (1873; 1325 Main Street) and Emmanuel United Presbyterian Church (1869–1871; 480 PA 519) in Eighty Four.
With the loss of the college, the area's economy shifted to coal and steel manufacturing in the late nineteenth and early twentieth centuries. During the 1820s, Canonsburg was a stagecoach stop on the Washington and Pittsburgh Turnpike, but it took rail access to Pittsburgh via the Pennsylvania Railroad's Chartiers Branch, established in 1871, to spark an economic recovery. The brick passenger station remains at Murdock and Jefferson streets (c. 1870). The railroad, combined with access to coal, spurred the development of ever-larger factories making sheet iron, bridges, pottery, and stoves, in addition to mining and coal shipping. By 1902, there were twelve trains a day through Canonsburg. The large brick PNC Bank (1903; 4 W. Pike Street) illustrates the commercial success of these enterprises. The borough's commercial core suffered through a period of demolitions in the late 1950s, leaving the brick Colonial Revival Municipal Building and Library of 1963 to act as a town center until the new library, at the corner of N. Jefferson Avenue and Murdock Street, designed by L. D. Astorino, is completed.
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