It was a railway station and had a post office between 1901 and 1936. It was named after explorer Nathaniel J. Wyeth, builder of Fort Hall (today's Pocatello, Idaho) and the Fort William trading post on Sauvie Island. The area is now home to the Wyeth State Recreation Area.
Wyeth was an early settlement site. It became the site of a Civilian Conservation Corps (CCC) camp in the 1930s. In the 1940s, it was the site of Camp 21, a Civilian Public Service camp for Conscientious Objectors that took over the abandoned CCC facility during World War II. Residents of the camp included architect Kemper Nomland, actor Lew Ayres, politician George Brown, Jr., and actor, director and playwright Kermit Sheets.
- "Wyeth". Geographic Names Information System, U.S. Geological Survey. November 28, 1980. Retrieved 2010-02-25.
- McArthur, Lewis A.; McArthur, Lewis L. (2003) [First published 1928]. Oregon Geographic Names (7th ed.). Portland, Oregon: Oregon Historical Society Press. pp. 1060–1061. ISBN 9780875952772. OCLC 53075956.
- Wyeth Columbia River Images
- Wyeth Columbia River Gorge National Scenic Area
- Charles Davis and Jeffrey Kovac Confrontation at the Locks; A Protest of Japanese Removal and Incarceration during World War II, Oregon Historical Quarterly
- Jeffrey Kovac, Refusing War, Affirming Peace: A History of Civilian Public Service Camp #21 at Cascade Locks, Oregon State University Press, 2009