Grant County was established on October 14, 1864, from parts of Wasco and Umatilla counties. Prior to its creation, cases brought to court were tried in The Dalles, county seat of the vast Wasco County. The great distance to The Dalles made law enforcement a difficult problem, and imposed a heavy burden on citizens who had a need to transact business at the courthouse.

After gold was discovered in 1862 on Whiskey Flat, it has been estimated that within ten days 1,000 miners were camped along Canyon Creek. This increased population created a need for county government. Over $20 million in gold was mined from the Canyon City and Susanville areas before the inevitable exhaustion of the deposits.

At the time of its creation, Grant County was the largest county in the state. Its size was later reduced by the transfer of land to Lake County and the creation of Harney and Wheeler Counties.