Calaveras County was one of the original counties of California, created in 1850 at the time of statehood. Parts of the county's territory were given to Amador County in 1854 and to Alpine County in 1864.

The meaning of the word calaveras is "skulls." This county takes its name from the Calaveras River which was reportedly so designated by Spanish explorer Gabriel Moraga when he found, on the banks of the stream, many skulls of Native Americans who had either died of famine or had been killed in tribal conflicts over hunting and fishing grounds.