The area was long inhabited by the Tongvapeople (or "People of the Earth"), who were later renamed the Gabrieleños by the Spanish missionaries, after the nearby Mission San Gabriel Arcángel.

In 1798, José María Verdugo, a corporal in the Spanish army from Baja California, received theRancho San Rafael from Governor Diego de Borica, formalizing his possession and use of land on which he had been grazing livestock and farming since 1784. Rancho San Rafael was a Spanish concession, of which 25 were made in California. Unlike the later Mexican land grants, the concessions were similar to grazing permits, with the title remaining with the Spanish crown.

In 1860 His grandson Teodoro Verdugo built the Verdugo Adobe, which is the oldest building in Glendale. The property is the location of the Oak of Peace where early Californio leaders including Pio Pico met in 1847 and decided to surrender toLieutenant Colonel John C. Frémont.

Verdugo's descendants sold the ranch in various parcels, some of which are included in present-day Atwater Village, Eagle Rock, and Highland Parkneighborhoods of Los Angeles.

In 1884, residents gathered to form a town and chose the name "Glendale". Residents to the southwest formed "Tropico" in 1887. The Pacific Electric Railwaybrought streetcar service in 1904.