The settlement of Indigenous Californians in the modern Los Angeles Basin and the San Fernando Valley was dominated by the Tongva (now also known as the Gabrieleño since the era of Spanish colonization).

The historic center of Tongva power in the region was the settlement of Yaanga (Tongva: Iyáangẚ), meaning "place of the poison oak", which would one day be the site where the Spanish founded the Pueblo de Los Ángeles. Iyáangẚ has also been translated as "the valley of smoke".

Maritime explorer Juan Rodríguez Cabrillo claimed the area of southern California for the Spanish Empire in 1542, while on an official military exploring expedition, as he was moving northward along the Pacific coast from earlier colonizing bases of New Spain in Central and South America. Gaspar de Portolà and Franciscan missionary Juan Crespí reached the present site of Los Angeles on August 2, 1769. 

New Spain achieved its independence from the Spanish Empire in 1821, and the pueblo now existed within the new Mexican Republic. During Mexican rule, Governor Pío Pico made Los Angeles the regional capital of Alta California.

By this time, the new republic introduced more secularization acts within the Los Angeles region. In 1846, during the wider Mexican–American War, marines from the United States occupied the pueblo.

This resulted in the siege of Los Angeles, where 150 Mexican militias fought the occupiers, who eventually surrendered.

Los Angeles’s metamorphosis to world-class metropolis began in the 1870s. Its first leap into the modern era came in 1876, when the Southern Pacific Railroad completed a rail hookup with San Francisco.

Also during that decade, the city experienced a boom based on the arrival of newcomers seeking a healthy climate. Called “the Sick Rush,” it was one of the first of many booms that have punctuated the history of Los Angeles.

Another decisive step toward creating a metropolis was the development of a system that would import enough water from the eastern slopes of the Sierra Nevada to sustain a population of millions in the Los Angeles area.

The designer of the Los Angeles Aqueduct was a self-trained, Irish-born water engineer, William Mulholland, who also oversaw its construction.

The project (1904–13) involved aggressive dealings with ranchers and business owners in the Owens Valley, the work of some 4,000 labourers, and the invention and application of new technologies, including the Caterpillar tractor.

The water was propelled entirely by gravity, coursing through open canals, pipes, and tunnels onto a spillway in the San Fernando Valley.