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Sailing his flagship San Salvador from Navidad, New Spain, Cabrillo claimed the bay for the Spanish Empire in 1542, and named the site "San Miguel".

In November 1602, Sebastián Vizcaíno was sent to map the California coast.

In 1821, San Diego became part of the newly independent Mexico, which reformed as the First Mexican Republic two years later.

California became part of the United States in 1848 following the Mexican–American War and was admitted to the union as a state in 1850.

It is part of the San Diego–Tijuana conurbation, the second-largest transborder agglomeration between the US and a bordering country after Detroit–Windsor, with a population of 4,922,723 people.

The city is known for its mild year-round climate, natural deep-water harbor, extensive beaches, long association with the United States Navy, and recent emergence as a healthcare and biotechnology development center.

The city is the seat of San Diego County and is the economic center of the region as well as the San Diego–Tijuana metropolitan area.