It is bordered by Woodland Hills on the south, West Hills on the west, Chatsworth on the north, and Winnetka on the east.

The area of present day Canoga Park was the homeland of Native Americans in the Tongva-Fernandeño and Chumash-Venturaño tribes, that lived in the Simi Hills and along to the tributaries of the Los Angeles River. They traded with the north Valley Tataviam-Fernandeño people. Native American civilizations inhabited the Valley for an estimated 8,000 years. Their culture left the Burro Flats Painted Cave nearby.

From 1797 to 1846 the area was part of Mission San Fernando Rey de España (Mission San Fernando). After the Mexican War of Independence from Spain the 'future Canoga Park' land became part of Rancho Ex-Mission San Fernando. In 1845 a land grant for the separate and historically rich Rancho El Escorpión was issued by Governor Pío Pico to three Chumash people, Odón Eusebia, his brother-in-law Urbano, and Urbano's son Mañuel. It was located in the area west of Fallbrook Avenue, and later called Platt Ranch.

In 1863 the syndicate San Fernando Homestead Association led by Isaac Lankershim and Isaac Van Nuys purchased the southern half of the historic San Fernando Valley. They established seven wheat ranch operations and were the first to ship wheat to Europe from California. In 1869 Alfred Workman acquired the westernmost ranch, a 13,000 acres (50 km2) wheat farm in future Canoga Park (for more: See Landmarks section below). Eucalyptus trees first imported and planted on the ranch, spread to other Canoga Park area ranches and farms.

The area was included in the greater part of the southern San Fernando Valley development syndicate, started when the LA Suburban Home Company bought out the Van Nuys Ranch in l909. The entire south San Fernando valley, from Roscoe Bl south to the hills, with certain exceptions, were to be subdivided on anticipation of the Los Angeles aqueduct's completion in 1913. The purchasers of the land included Harry Chandler and Harrison Gray Otis of the Los Angeles Times, Moses Sherman (a streetcar line builder), and Hobart Johnstone Whitley, an all purpose real estate developer who, from a start in the Land Rush of l889 in Oklahoma to platting out l40 towns, including Hollywood.

The area was originally named Owensmouth (Pacific Electric) by Los Angeles Suburban Home Company by general manager Hobart Johnstone Whitley with a real estate salesman's exaggeration that it was the new mouth of the Owens River, after the Los Angeles Aqueduct would be completed the next year. The town was founded on March 30, 1912, and the Suburban Home Company contracted with the Janss Investment Company, to sell properties. A well-thought pre-development scheme brought Pacific Electric streetcars and an all purpose highway (Sherman Way) out all the way from Hollywood through Cahuenga Pass, through the previously subdivided Van Nuys (l911). Highlighting the "opening day barbecue" was the display of the "Owensmouth Baby", a racecar that could go up and down the paved Sherman Way at the incredible speed of 35 mph—as you could do—in an age without pavement nor speed limits.

Owensmouth, as the junior San Fernando Valley city to Van Nuys, promoted itself with the "baby" motif—using storks in their advertisement—the "baby city" of the Valley. And Owensmouth remained a very small community.

The lack of an independent water supply made annexation to the City of Los Angeles inevitable, and on February 26, 1917 it joined with its larger neighbor. The name was changed to Canoga Park in 1930. It is believed to be named after Canoga, New York, which derived its name from the Native American village "Ganogeh". Eventually, the area's zoning was rural/agricultural and its industry was small farms involved in production of fruits, vegetables, melons, some livestock, horses, movie/television studio and stunt location work.

In 1955, Rocketdyne, then a division of North American Aviation, moved into the area. It became a major employer along with the Atomics International and Santa Susana Field Laboratory (SSFL) divisions. Other aerospace companies followed: including Atomics International, Thompson Ramo Wooldridge-TRW, Hughes Aircraft, Rockwell International, Boeing, and Teledyne. Small machine shops and other ancillary businesses also sprang up to service the aerospace industry. Currently the Pratt & Whitney Rocketdyne facility, operated by Pratt & Whitney division of United Technologies Corporation, is the remaining aerospace industry. The Santa Susana Field Lab property has been closed and will be undergoing an extensive environmental cleanup, and become an open-space park.

In 1987 much of the western district of Canoga Park was renamed West Hills and a portion of the eastern district was renamed Winnetka. On June 25, 2005, Canoga Park was named an All-America City. Currently Canoga Park and neighboring Woodland Hills may have the largest shopping mall on the West Coast, with the planned merger of Topanga Plaza-Westfield Topanga with the Woodland Hills Promenade-Westfield Promenade in Warner Center.