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The first humans to arrive in what is now Spokane County arrived between 12,000 and 8,000 years ago and were hunter-gatherer societies who lived off the plentiful game in the area. Initially, the settlers hunted predominantly bison and antelope, but after the game migrated out of the region, the native people became dependent on gathering various roots, berries, and nuts, and harvesting fish. The Spokane tribe, after which the county is named, means "Children of the Sun" or "sun people" in Salishan Explorer-geographer David Thompson, working as head of the North West Company's Columbia Department, became the first European to explore what is now the Inland Northwest. After establishing the Kullyspell House and Saleesh House fur trading posts in what are now Idaho and Montana, Thompson then attempted to expand further west. He sent out two trappers, Jacques Raphael Finlay and Finan McDonald, to construct a fur-trading post on the Spokane River in Washington and trade with the local Indians. This post was established in 1810, at the confluence of the Little Spokane and Spokane Rivers, becoming the first enduring European settlement of significance in Washington. Known as the Spokane House, or simply "Spokane", it was in operation from 1810 to 1826.
Spokane County was established by the Washington legislature effective January 29, 1858. It was annexed by Stevens County on January 19, 1864, and recreated on October 30, 1879. The first post office in the county was located at Spokane Bridge. The current Spokane county seat holder, Spokane, wrested the seat from Cheney in 1886.