Three European events indirectly triggered the exploration of today's California. First, the Danish-born Russian cartographer and explorer Vitus Bering (Ivan Bering in Russia) led two "Kamchatka" expeditions, the second one in 1733 also known as the "Great Northern Expedition" to map the eastern shores of Siberia and the western shores of North America. In 1728 he "discovered" the strait that bears his name between Russia and Alaska just before dying. News of Russian traders venturing south along the coast alarmed Spain. In 1732 Mikhail Gvozdev became the first Russian to cross the strait from Asia to America. Second, at the end of the Seven Years' War (1756–1763), during which Spain momentarily lost both Cuba and the Philippines (which it regained by giving Britain its other colony of Florida), but gained the vast French colony of Louisiana extending all the way to the Mississippi River, the king of Spain launched reforms throughout the empire. His emissary Jose' de Galvez was dispatched to Nueva Espana in 1765 and set out to improve the government of the colony. Galvez did more. He dreamed of colonizing California and prepared to launch expeditions both overland and by sea. Third, in 1767 Spain decided to expel the Jesuits from its empire, following the example of Portugal (1759) and France (1764): the Jesuits had become too powerful, too rich, and too political, and in America they often protected the indigenous populations against the European colonizers. The king dispatched Gaspar de Portola to Nueva Espana to turn over the 15 missions created by the Jesuits in Baja California to the Franciscan friars, and Junipero Serra (a friar who refused to ride horses and insisted on walking, who in the 1750s had conceived some celebrated missions in the Sierra Gorda of Queretaro) was placed in charge of the missions. Galvez appointed Portola as "governor" of Las Californias (plural), dividing the region into Antigua and Nueva California, respectively the one that had been explored and the one in the north that was still unexplored. Antigua (essentially the peninsula) came to be known as Baja California, and Nueva came to be known as Alta California. The latter presented natural obstacles to exploration from the south: the overland route was rugged along the coast and tough inland (deserts and mountains), not to mention Indian resistance, and the sea route ran counter to the southerly currents of the Pacific coast. In 1769 Galvez was ready to launch two expeditions up the coast of Alta California, one overland, led by Portola, and one by ship, led by Vicente Vila. Galvez drafted Junipero Serra's Franciscan friars to accompany the expeditions. The two groups departed from Baja California and met in San Diego and then continued overland, preceded by soldiers led by Fernando Rivera y Moncada and Franciscan diarist Juan Crespi'. Junipero Serra founded the mission of San Diego in July 1769. Portola "discovered" on foot the San Francisco Bay in November (spotting it from today's Sweeney Ridge). In 1770 Junipero Serra sailed to Monterrey and established the mission of San Carlos Borromeo de Carmelo (today's Carmel, near today's Monterey) while at the same time Portola marched back to Vizcaino's Monterrey Bay and established a port and a "presidio" (a fort and a village). Thus was Monterrey founded (now known as Monterey).

Meanwhile, Galvez had fallen sick and returned to Spain in 1771. Serra's friars founded other missions, notably San Gabriel Arcangel (near today's Los Angeles) in 1771 and San Luis Obispo de Tolosa in 1772. The old missions of Baja California were now run by the Dominicans. In 1773 a border was drawn between "Franciscan" California and "Dominican" California, de facto the border between Alta and Baja California. In 1774 Spain finally appointed a governor of Las Californias: Felipe de Neve y Padilla, who took residence in Baja California. In 1774 Fernando Rivera y Moncada, who had been second-in-command on the Portola expedition, traveled again to Monterrey because he had been appointed military commander, arriving in May 1774. In November 1774 the first baby of European immigrants (the first "white" baby) was born in Alta California: Juan Jose' Garcia, the son of a mission blacksmith. The next major explorer was Juan Bautista de Anza, who differed from his predecessors in one simple fact: he was born in Nueva Espana, not in Spain. He set out in 1774 and, after following an easier inland route instead of the rugged coastal route, in 1776 he established the Presidio of San Francisco near the strait that today is called "Golden Gate" (the narrow entrance to the bay) and founded the town of San Jose' de Guadalupe (today's San Jose). The DeAnza group consisted of almost 100 people, which almost doubled the Spanish population of Alta California: that's how small the Spanish footprint was in this province of Nueva Espana. Serra's friars founded the mission of San Francisco de Asis in 1776 and the mission of Santa Clara de Asis in 1777. Halfway between the presidio and the mission DeAnza created the settlement of Yerba Buena, the beginning of the city of San Francisco (Yerba Buena is today's Portsmouth Square in Chinatown).

The Franciscan missions were connected by an overland route which became known as the "Camino Real". In 1775 Juan de Ayala became the first explorer to sail into the San Francisco Bay, passing through the future Golden Gate. His cartographer Jose' de Canizares drew the first map of the Bay. Both Anza and Ayala had been sent by Spain for fear that Russians were colonizing the region. In 1776 Spain declared Monterrey the capital of both Baja and Alta California, and governor Felipe de Neve moved to Monterrey. El Pueblo de Nuestra Senora la Reina de los Ángeles de Porciuncula (today's Los Angeles) was instead founded in 1781 by order of governor Felipe de Neve after the king of Spain in person requested that more secular villages be established in Alta California. Neve populated this place located near the San Gabriel mission with a group of 40 or 50 immigrants from distant parts of Mexico, recruited by Rivera, who travelled more than 1,500 kilometers to settle such a distant and dangerous place (Rivera didn't make it back because he was killed by Yuma Indians along the way). Within eight years the five main explorers were all dead: Rivera was killed in 1781, Serra died in 1784, Portola in 1786, Galvez in 1787, and Anza in 1788.

After San Jose and Los Angeles, the third secular pueblo founded by the Spanish colonial government of Alta California was Villa de Branciforte, near today's Santa Cruz, established in 1797. The two provinces of Las Californias (Alta and Baja) were officially created in 1804. The Mexican-born explorer Gabriel Moraga explored the Central Valley of California between 1806 and 1808, and named both the Sacramento Valley and the Sacramento River. Alta California also included Nevada, Utah and parts of Arizona, New Mexico, western Colorado and southwestern Wyoming.