Gilliam County was established in 1885 from a portion of Wasco County and was named after Col. Cornelius Gilliam, a veteran of the Cayuse Indian War. The first county seat was at Alkali, now Arlington. At the general election of 1890, voters chose to move the county seat to Condon, known to early settlers as "Summit Springs." A brick courthouse was built in Condon in 1903 but was destroyed by fire in 1954. The present courthouse, built on the same site, was constructed in 1955.

Gilliam County is in the heart of the Columbia Plateau wheat area. The economy is based mainly on agriculture, with an average farm size of about 4,200 acres. Wheat, barley and beef cattle are the principal crops. The largest individual employers in the county are two subsidiaries of Waste Management Inc., Chemical Waste Management of the Northwest and Oregon Waste Systems, Inc., two regional state-of-the-art waste disposal landfills.

With elevations of over 3,000 feet near Condon in the south of the county and 285 feet at Arlington, 38 miles north, the county offers a variety of climates and atmosphere. Hunting, fishing and tourism are secondary industries. Two major rivers, the John Day and Columbia, traverse the area east-to-west, as well as Interstate 84. Highway 19 connects the county's major cities north-to-south and serves as gateway to the John Day Valley.