What is now known as El Dorado County has been home to the Maidu, Nisenan, Washoe, and Miwok Indigenous American nations for centuries. Because of colonization, their numbers dropped severely.

A settler looking to start a company processing cut trees found gold on the land he started using. The region became famous for being the site of the 1848 gold discovery that sparked the California Gold Rush.[6] The County of El Dorado was one of California's original 27 counties created effective February 18, 1850 (the number has risen to 58 today). Its name is derived from the Spanish meaning "the gilded/golden".

The final segments of the Pony Express mail route ran through El Dorado County until its replacement with the telegraph service in 1861

The Caldor Fire started on August 14, 2021, near Little Mountain, south of Pollock Pines in El Dorado County, about two miles East of Omo Ranch and four miles south of Grizzly Flats. It initially burned slowly, but exploded in size on August 16 due to high winds. By the night of August 16 it was 6,500 acres. On August 17 the fire grew to 30,000 acres as it expanded rapidly north and east, crossing the North Fork Cosumnes River and approaching Sly Park Reservoir. By August 20 the fire had burned nearly to Highway 50, forcing a closure of the highway. Over the next few days, the fire crossed Highway 50 in the vicinity of Kyburz. Starting on August 27 winds drove the fire rapidly east towards the Lake Tahoe Basin. By August 30, it had reached Echo Summit, less than 5 miles from South Lake Tahoe. As of October 24, 2021, it had burned 221,775 acres. The cause of the fire is currently under investigation and full containment was reached on October 21.