The Port of San Diego lies on the Pacific shores of San Diego Bay in Southern California just 12 kilometers north of the United States' border with Mexico. Located some 96 nautical miles southeast of the country's largest Port of Los Angeles, the Port of San Diego has one of the finest natural deep-water harbors in the world. Nearly landlocked, the Port of San Diego is protected by two peninsulas that separate it from the Pacific Ocean. The Port of San Diego Bay is a busy international shipping center and home to a complex of military bases. The Port of San Diego is the ninth biggest city in the United States and the second biggest city in California. In 2005, over 1.2 million people lived in the Port of San Diego, and over 2.9 million lived in the San Diego-Carlsbad-San Marcos metropolitan area.

The Port of San Diego is based on three major economic sectors: defense, manufacturing, and tourism. In addition, the city contains a growing biotechnology and research industry. In 2004, the Milken Institute ranked the Port of San Diego as the top biotech cluster in the United States. Companies that created wireless cellular technology (like Qualcomm) are based in the Port of San Diego. The city's economy is greatly influenced by the Port of San Diego. It contains the US West Coast's only major ship-building and submarine yards, and the Port of San Diego houses the world's biggest naval fleet. It is also the base for several major national defense contractors. Located near Mexico, tourism is an important part of the Port of San Diego's economy, and it is home to some great beaches as well as several popular amusement parks.

For over ten thousand years, the Kumeyaay Indians have inhabited the area of today's Port of San Diego. The first Europeans arrived there in 1542 when explorer Juan Rodriguez Cabrillo claimed the bay for Spain, naming the site San Miguel. Sebastian Vizcaino arrived there in 1602 when he was tasked with mapping the California coast. He surveyed the harbor area and named it San Diego after the Catholic Saint Didacus.

In 1769, the Fort Presidio of San Diego was established by Gaspar de Portola, and Franciscan friars founded the Mission San Diego de Alcala. By the late 1700s, the mission had the biggest population of indigenous peoples in Alta California, including more than 1400 newly-ordained priests. The Port of San Diego was California's southern stop on the famous and historic El Camino Real.

When the Viceroyalty of New Spain won its independence, becoming Mexico, the Mission San Diego de Alcala in the future Port of San Diego went into decline when mission lands were taken from the church by Mexican law. Yet it is still an active Catholic church today and a National Historic Landmark in the Port of San Diego.

In 1847, the Mormon Battalion (the US's only religious military unit) marched to the Port of San Diego during the Mexican-American War. Some of its members constructed the first courthouse and a brickyard in what would become the Port of San Diego's Old Town. During the Mexican-American War, the Battle of San Pasqual was fought in what is now part of the city.

After the war and during the California Gold Rush, Americans began to migrate to the Port of San Diego. California was admitted to the Union of the United States, and the Port of San Diego was incorporated as a city in 1850. The first city charter was adopted by the Port of San Diego in 1889.

The first site of San Diego was inland at Presidio Hill, far from navigable waters. Alonzo Horton encouraged the development of a "New Town" to the south in what was to become the Port of San Diego's downtown. Due to its convenient location on San Diego Bay, people and businesses quickly moved to the new site which became the Port of San Diego's economic and power center.

In the early 20th Century, the Port of San Diego played host to two World's Fairs, the Panama-California Exposition of 1915 and the California Pacific International Exposition of 1935. Many of today's Spanish-Baroque buildings in the Port of San Diego's Balboa Park were created for these fairs, even though they were meant to be temporary. Most of the buildings were later rebuilt as they fell into disrepair to preserve this unique Port of San Diego architectural style.

In 1901, the Navy Coaling Station in the Port of San Diego's Point Loma was opened, establishing the U.S. Navy's presence in the Port of San Diego. During the 1920s, the naval complex grew significantly. After World War II, the local economy grew largely due to the activities of the U.S. military. However, after the Cold War ended, budget reductions for military operations seriously impacted local Port of San Diego aerospace and defense industries. City leaders began to seek a more diverse industrial base for the Port of San Diego, and it has since become an important center for the growing biotechnology industry.

In 2003, the Port of San Diego suffered the famous Cedar Fire, the biggest wildfire in California for the past 100 years. Burning over 113 thousand hectares, the fire took 15 lives and destroyed over two thousand homes. Schools were closed for a week, and the emergency rooms served thousands suffering from asthma, respiratory problems, and smoke inhalation. In 2007, the Port of San Diego was struck again by wildfires that raged through the city and county.

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