Native Americans, including the Methow people, were the first inhabitants of Winthrop, with evidence of human habitation at least 8,000 to 10,000 years before present.

[3] They lived along the banks of the Methow, Twisp, and Chewuch rivers, digging camas root, picking berries, fishing, and hunting.

[3] The town's first trading post and general store was opened in 1892 by Guy Waring of Boston, who moved with his family to the confluence of the Chewuch and Methow rivers a year before.

[3] Waring later formed the Methow Trading Company and established several businesses; his family settled into the "Castle" (now the Shafer Museum).

[5] Waring's original Duck Brand Saloon was built in 1891; it survived the fire and is now Winthrop's Town Hall.

Winthrop's industry at this time consisted of a well-equipped sawmill, several dairies, raising cattle, and supplying the local mines with goods.

[6] Owen Wister, Waring's Harvard University roommate, wrote The Virginian, America's first western novel, after honeymooning in Winthrop.

[4][5] Winthrop and the surrounding valley was incorporated into the Washington Forest Reserve by an executive order signed by President Grover Cleveland on February 22, 1897.

[citation needed] The first plans to build an automobile road across the North Cascades from Bellingham Bay to the Columbia River were approved by the state legislature in 1893.

[3][11] A two-block section of downtown was rebuilt to use 1890s Old West architecture, including false fronts and a boardwalk; by September 1972, 22 buildings had been remodeled.

Like most of the Inland Northwest, Winthrop has a humid continental climate (Köppen Dsb), with cold, snowy winters and very warm summers with cool nights and little rainfall.