Santa Clara County was one of the original counties of California, formed in 1850 at the time of statehood. Part of the county's territory was given to Alameda County in 1853.

The county is named after Mission Santa Clara, which was established in 1777, and named for Saint Clare of Assisi, Italy. The name "Clare" or "Clara" means "clear" or "bright."

In 1882, Santa Clara County tried to levy taxes upon property of the Southern Pacific Railroad within county boundaries. The result was the U.S. Supreme Court case of Santa Clara County v. Southern Pacific Railroad, 118 U.S. 394 (1886), in which the Court extended Due Process rights to artificial legal entities.

In the 1980's and 1990's, many hi-tech companies began operations in Santa Clara County, which became the headquarters for such companies as Apple Computer, Hewlett Packard, Quest, Intel, and many others. Today the county is the main area of the Silicon Valley, which includes several other counties both north and south of Santa Clara. Some tribes of the Ohlone Indians lived at Coyote Creek in Santa Clara.