The town was originally called Samuel's Creek after the discovery of Muddy Creek by Samuel Germein. In 1846, Port Pirie Creek was named by Governor Robe after the John Pirie, the first vessel to navigate the creek when transporting sheep from Bowman's Run near Crystal Brook. In 1848, Matthew Smith and Emanuel Solomon bought 85 acres (34 ha) and subdivided it as a township to be known as Port Pirie.
On 28 September 1876, Port Pirie was declared a municipality, with a population of 947. With the discovery of rich silver-, lead- and zinc-bearing ore at Broken Hill in 1883, and the completion of a narrow gauge railway from Port Pirie to close to the Broken Hill field in 1888, the economic activities of the town shifted. In 1889 a lead smelter was built by the British Blocks company to treat Broken Hill ore. Broken Hill Proprietary initially leased the smelter from British Blocks and then began constructing their own smelter from 1892. In 1915 the smelter was taken over by a major joint venture of Broken Hill-based companies, Broken Hill Associated Smelters (BHAS). Led by the Collins House Group, BHAS became the biggest lead smelter in the world by 1934.
The smelter gradually passed to Pasminco, then Zinifex, and is now operated by Nyrstar. By 1921 the town's population had grown to 9801 living in 2308 occupied dwellings. By this date there were also 62 boarding houses to cater for the labour demands at the smelter and on the increasingly busy waterfront. Port Pirie was declared South Australia's first provincial city in 1953, and today it is South Australia's second largest port. It is characterised by a gracious main street and some interesting and unusual historic buildings.
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