Jesuit missionary Eusebio Francisco Kino visited the Santa Cruz River valley in 1692, and founded the Mission San Xavier del Bac in 1700 about 7 mi (11 km) upstream from the site of the settlement of Tucson.

A separate Convento settlement was founded downstream along the Santa Cruz River, near the base of what is now "A" mountain.

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The Tucson MSA forms part of the larger Tucson-Nogales combined statistical area (CSA), with a total population of 1,010,025 as of the 2010 Census.

Tucson is the second-largest populated city in Arizona behind Phoenix, both of which anchor the Arizona Sun Corridor.

Over the following years, the city continued to grow, with the population increasing to 20,292 in 1920 and 36,818 in 1940.

In 2006, the population of Pima County, in which Tucson is located, passed one million, while the City of Tucson's population was 535,000.

Hugo O'Conor, the founding father of the city of Tucson, Arizona authorized the construction of a military fort in that location, Presidio San Agustín del Tucsón, on August 20, 1775 (near the present downtown Pima County Courthouse).

During the Spanish period of the presidio, attacks such as the Second Battle of Tucson were repeatedly mounted by Apaches.

In 1885, the University of Arizona was founded as a land-grant college on over-grazed ranch land between Tucson and Fort Lowell. Veterans Administration had begun construction on the present Veterans Hospital.

In 1890, Asians made up 4.2% of the city's population. The population increased gradually to 13,913 in 1910. Many veterans who had been gassed in World War I, and were in need of respiratory therapy, began coming to Tucson after the war, because of the clean dry air.

John Clum, of Tombstone, Arizona fame was one of the passengers. Fort Lowell, then east of Tucson, was established to help protect settlers from Apache attacks.