The county derives its name from the Merced River, or El Río de Nuestra Señora de la Merced (River of Our Lady of Mercy), named in 1806 by an expedition headed by Gabriel Moraga, which came upon it at the end of a hot dusty ride on the El Camino Viejo across the San Joaquin Valley in Spanish colonial Las Californias Province.

Between 1841 and 1844, during the period when Alta California was a territory of independent Mexico, four Mexican land grants were made in what became Merced County: Rancho Orestimba y Las Garzas, Rancho Panoche de San Juan y Los Carrisolitos, Rancho San Luis Gonzaga, and Rancho Sanjon de Santa Rita

Merced County was formed in 1855 from parts of Mariposa County. Parts of its territory were given to Fresno County in 1856.