The John Day basin remained largely unexplored by non-natives until the mid-19th century. Lewis and Clark noted but did not explore the John Day River while traveling along the Columbia River in 1805.

In the 1840s, thousands of settlers, attracted in part by the lure of free land, began emigrating west over the Oregon Trail. Leaving drought, worn-out farms, and economic problems behind, they emigrated from states like Missouri, Illinois, and Iowa in the Midwest to Oregon, especially the Willamette Valley in the western part of the state. After passage of the Homestead Act of 1862 and the discovery of gold in the upper John Day basin, a fraction of these newcomers abandoned the Willamette Valley in favor of eastern Oregon.

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