Located at the point where the Conemaugh River and Loyalhanna Creek meet to form the Kiskiminetas River, Saltsburg was settled in 1766. The town was laid out in 1817, three years after the first salt well was bored by William Johnson. Salt production peaked in 1838, when more than thirty wells produced over 70,890 bushels. The largest well, the Great Conemaugh Salt Works, was two miles east of the village. Fuel to power the pumps for the saltworks sparked the coal mining industry in the southern part of the county.
The Pennsylvania Canal and the Pennsylvania Railroad both traversed the borough. Three five-bay stone houses dating from the 1830s and early 1840s line the canal's former path, which today is a borough park. The Saltsburg Historical Society (105 Point Street) is located in a house built between 1830 and 1839 that is typical of these canal-era houses: flush with the sidewalk, two stories, five bays, and a central door. The stone house at 214 Washington Street is also in excellent condition. The third stone house, known as the McIlvain house at 519 Salt Street, has a Greek Revival portico that was added in 1910. After the railroad withdrew in 1954, business slowed. Most of the nineteenth-century building fabric survives and is preserved as a historic district. Saltsburg's location at the confluence of two water systems has made it both a tourist attraction and a frequent victim of floods. Eight large dams throughout the county (on Conemaugh River and Loyalhanna, Yellow, and Little Mahoning creeks) have helped to regulate the waters and create recreational facilities nearby.
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