The area was long inhabited by the native Kumeyaay people (also known as the Diegueño by the later Spanish settlers), who lived off the land and created a proud culture. The first time a European visited the region was in 1542, when Portuguese explorer Juan Rodriguez Cabrillo, sailing under the Spanish Flag, claimed the bay for the Spanish Empire and named the site San Miguel.

In November of 1602, Sebastián Vizcaíno was sent to map the California coast. Arriving with his flagship "San Diego", Vizcaíno surveyed the harbor and what is now Mission Bay and Point Loma, renaming the area for the Spanish Catholic Saint, St. Didacus (more commonly known as San Diego).

San Diego was established in 1769 as the first Spanish mission in California, at the present site of Old Town. However, due to the poor nature of soils in the Old Town area, the mission was eventually relocated about five miles up river in Mission Valley.

In the 19th century, San Diego passed from Spanish to Mexican to American hands. In 1850, a few years after the United States gained control of California, San Diego was officially designated a city. But with much of the westward expansion to California centered on the gold rush and San Francisco, American influences were slow to come to San Diego. Eventually they did, however, and in the later decades of the 19th century the railroad came to San Diego, resulting in further growth of the city and the establishment of Downtown and its surrounding neighborhoods.

The U.S. Navy discovered San Diego in the early 20th century, and constructed a coaling station on Point Loma in 1907. Ten years later, the Naval Air Station on Coronado island was established, and in later years the Navy would take on an increasingly important role in the city's economy. Today San Diego is home to the Navy's Pacific Fleet, and is a favorite leave location for sailors.

San Diego has 1.3 million people and serves as a hub for bio technologies and communication tech. San Diego's also benefits from tourism and conventions. The city is also becoming a favorite for those who are looking to take advantage of the climate for athleticism, and using a bicycle as a means of transportation, see By Bike section.