In 1565, the Spanish developed a trading route where they took gold and silver from the Americas and traded it for goods and spices from China and other Asian areas. The Spanish set up their main base in Manila in the Philippines. The trade with Mexico involved an annual passage of galleons. The Eastbound galleons first went north to about 40 degrees latitude and then turned east to use the westerly trade winds and currents. These galleons, after crossing most of the Pacific Ocean, would arrive off the California coast 60 to over 120 days later, near Cape Mendocino, about 300 miles (480 km) north of San Francisco, at about 40 degrees N. latitude. They could then sail south down the California coast, utilizing the available winds and the south-flowing California Current, about 1 mi/hr (1.6 km/h). After sailing about 1,500 miles (2,400 km) south on they eventually reached their home port in Mexico. By 1700 the galleons' route turned south farther offshore and reached the California coast south of Point Conception. Often they did not land, because of the rugged, foggy coast, and they could not risk the treasure they carried.

Spain wanted a safe harbor for galleons enroute from Manilla to Acapulco. They did not find San Francisco Bay, perhaps because of fog hiding the entrance. In 1585 Gali charted the coast just south of San Francisco Bay, and in 1587 Unamuno explored Monterey Bay or Morro Bay, marking the first time in modern history when Asians (Filipino crewmen) set foot on what would be the United States. In 1594 Soromenho explored and was shipwrecked in Drake's Bay just north of San Francisco Bay, then went south in a small boat past Half Moon Bay and Monterey Bay. They traded with Native Americans for food.