The Umatilla National Forest takes its name from the Umatilla Indian word meaning "water rippling over sand." Explorers Lewis and Clark passed through the area in 1805 on the Columbia River, and Marcus and Narcissa Whitmanpassed through in 1836 to establish a mission at Wailatpu near Walla Walla, Washington. Thousands of emigrants later followed the Oregon Trail west, and many remained in the Blue Mountain region. Discovery of gold in Oregon in 1851 led to the settlement of the North Fork John Day River area. More than $10 million in gold and silver were mined, and remnants of the era are still visible in the National Forest. Some claims are still being mined.
Umatilla was established on July 1, 1908 from part of Blue Mountains National Forest and all of Heppner National Forest. Wenaha National Forest was added on November 5, 1920.
The forest was the site of the School Fire, the largest fire in the contiguous United States of 2005.