Tulare County was formed from parts of Mariposa County in 1852. Parts of the county's territory were given to Fresno County in 1856, to Kern County in 1866, to Inyo County in 1866 and Kings County in 1893.
Comandante Pedro Fages, while hunting for deserters in 1772, discovered a great lake surrounded by marshes and filled with rushes which he named Los Tules (the tules). It is from this lake that the county derives its name. The root of the name Tulare is found in the Mexican word tullin, designating cattail or similar reeds.
The infectious disease Tularemia caused by the bacterium Francisella tularensis is named after Tulare County.