Among the Native American tribes who lived in what is now Oregon were the Cayuse, Chinook, Clackmas, Coos, Klamath, Modoc, Molalla, Multnomah, Nez Perce, Paiute, Santiam, Siuslaw, Tillamook, Umatilla, Umpqua, and Willamette.

European explorers, primarily from England and Spain, are thought to have sailed along the Oregon coast in the 16th and 17th Centuries, looking for the Northwest Passage. Juan Rodriguez Cabrillo, who explored much of California, saw souther Oregon in 1543; other Spanish explorers followed. England's Sir Francis Drake is thought to have seen the coastline, and Captain James Cook charted the coastline in 1778.

American Captain Robert Gray in 1792 discovered what he called the Columbia River, naming it after his ship. Hearing of this discovery inspired President Thomas Jefferson to send the Corps of Discovery, led by Meriwether Lewis and William Clark to the area. They arrived in 1805, following the Columbia River to its mouth at the Pacific Ocean. They built Fort Clatsop to accommodate the winter that they stayed in the area.

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