Spain claimed California and began putting a series of missions in what was then called Alta California. The San Gabriel mission claimed lands in what is now the San Bernardino Valley, the Cajon Pass, and the San Gorgonio Pass. These lands were used for grazing of the large herds of cattle and sheep that belonged to the missions. The mission period ended when Mexico took over California from Spain by doling out the vast mission holdings to political favorites, wealthy people, and cronies of the governors of California in 1832. The "grants" were called ranchos, and many of the ranchos in San Bernardino County have lent their names to modern-day locales - Chino, Cucamonga, San Bernardino, and the San Gorgonio Pass.

In 1850, when the first California legislature met to divided the new state of California into its original 27 counties, the area that would become San Bernardino County was then in the huge San Diego County. A year later, it became part of the expanding Los Angeles County. During 1850 for a period of five years San Bernardino was an official Mormon settlement. In 1853, a bill was introduced to divide off the eastern portion of Los Angeles County and San Bernardino County was born. In the 1870's, navel oranges were planted at Riverside and became a prosperous business. Due to this over the next 30 years the San Bernardino Valley was opened up to several ventures these included Ontario, Upland, Fontan, Rialto, Highland, and Redlands. In the 1880's, gold was discovered in Bear and Holcomb Valleys in the San Bernardino Mountains, and opened up a surge of mining developments in the mountains and high desert which continue today.

Since its creation in 1872, San Bernardino County was divided 2 more times. A large portion in the north was given to Inyo County, and in 1893 the southernmost sliver was divided off to form part of Riverside County. San Bernardino County remains the largest county in the United States today.