Historically, the eastern Oregon region has been relatively isolated from Western Oregon. The first railroad connection from Portland, Oregon, crossing Eastern Oregon along the Columbia River through to the Union Pacific mainline in Granger, Wyoming, was completed in 1883, and the connection from the Willamette Valley over the Cascade Mountains at Willamette Pass was completed only in 1926 All-weather highways over the Cascade Mountains were not completed until the 1930s and 1940s.

Compared to the maritime rainforest climate of Western Oregon, which is adjacent to the Pacific Ocean, the climate of Eastern Oregon is a drier continental climate, with much greater seasonal variations in temperature. Unlike the Willamette Valley, Eastern Oregon gets a significant amount of snow in the winter. Some parts of Eastern Oregon get fewer than 10 inches of rain, and thus are considered deserts. Pine and juniper forests cover areas of Eastern Oregon, especially in the mountains east of Klamath Falls and in the Blue Mountains.