Eastern Oregon refers (roughly) to the eastern half of the state, from about Brothers onwards. Notable geographic features include the Columbia Plateau (in the north), the Blue Mountains (from the central to northeast part of the state), and the northern Great Basin (roughly the southeast quarter of the state).

Larger communities (still small) include Pendleton, Hermiston, Ontario, and La Grande.

Eastern Oregon is home to the largest known fungus on Earth - the "Humongous Fungus" honey mushroom, a small moose population in the far northeast near the Washington state border (Oregon's only moose herd), the stark Alvord Desert and Steens Mountain in the far southeast, and the westernmost extent of Greater Boise's Treasure Valley region.

This region is sparsely populated, with fewer than 200,000 people living in the counties generally considered to comprise the region. This is a smaller population than Eugene-Springfield.

The climate here is overall semi-arid in character, with sagebrush steppes, shortgrass prairies and sparse juniper and Ponderosa pine woodlands making up the majority of the region, but some areas being wetlands, true deserts and empty ephemeral lakes, and lush forested uplands that resemble the greener areas of the Cascades and Northern Rockies.

The people here tend to be more conservative and traditional than Western Oregon as a whole, albeit with a Western frontier individualist streak - similar to the intermountain West states further to the east.

The climate here is far drier than the western 30 percent of Oregon, with more continental variations. Winters are cold and in some areas snowy, summers have high daytime temperatures and chilly nights, and there is considerably more sunshine than west of the Cascade crest.