The Pomo, Coast Miwok and Wappo peoples were the earliest human settlers of Sonoma County, between 5000 to 8000 BC, effectively living within the natural carrying capacity of the land. Spaniards, Russians, and other Europeans claimed and settled in the county from the late 16th to mid 19th century, seeking timber, fur, and farmland. Sonoma was one of California's original counties, created at the time of statehood in 1850. It contains many historical monuments.

The Mission San Francisco Solano, founded in 1823 as the last and northernmost of 21 California missions, is in the present City of Sonoma, at the northern end of El Camino Real. El Presidio de Sonoma, or Sonoma Barracks (part of Spain's Fourth Military District), was established in 1836 by Comandante General Mariano Guadalupe Vallejo. His duties included keeping an eye on the Russian traders at Fort Ross, secularizing the Mission, maintaining cooperation with the Native Americans of the entire region, and doling out the lands for large estates and ranches. The City of Sonoma was the site of the Bear Flag Revolt in 1846.