On June 24, 1542, Juan Rodríguez Cabrillo departed the port of Navidad, Mexico, with his flagship and two other vessels, the La Victoria and the San Miguel. Three months later, on September 18, the expedition reached San Miguel, named after one of his ships. San Miguel is present-day San Diego Bay. Six days later, the fleet sailed north along the California coast, visiting islands and coastal villages near Santa Cruz, Catalina, and San Clemente, while recording their names and population counts.

On November 13, the Cabrillo expedition then moved north along the coast, where they sighted Port Reyes. Occasional autumn storms forced them to turn back south where they sailed to Monterey Bay.

While staying over at San Miguel, the Spaniards were attacked by the native Tongva warriors around Christmas Eve. Cabrillo stumbled over rugged rocks and broke his shin while trying to help his men. His injury was infected and he developed gangrene. Cabrillo died on January 3, 1543. He is said to have been buried on Catalina Island.

In mid-February, the expedition set sail again towards Oregon and then returned to Navidad in April 1543.