The Santa Ana River is the largest river of Southern California in the United States. Its drainage basin spans four counties. It rises in the San Bernardino Mountains and flows past the cities of San Bernardino and Riverside, before cutting through the northern tip of the Santa Ana Mountains and flowing southwest past Santa Ana to spill into the Pacific Ocean. The Santa Ana River is 96 miles (154 km) long, and drains a watershed of 2,650 square miles (6,900 km²).

For its size the Santa Ana drainage basin is quite diverse. It ranges from high peaks of inland mountains in the north and east, to the hot, dry interior and semi-desert basin, to flat coastal plains in the west. Its climates range from dry alpine to chaparral and desert, and the watershed as a whole is very arid. Relatively little water actually flows in the river or most of its tributaries. One of its largest tributaries, the San Jacinto River, rarely reaches the Santa Ana except in extremely wet years. The relative lack of vegetation also makes the river prone to flash flooding. Even so, a wide variety of animal and plant life has always been dependent on the river.

Santa Ana /ˌsæntə ˈænə/ is the county seat and second most populous city in Orange County, California, and with a population of 324,528 at the 2010 census, Santa Ana is the 57th-most populous city in the United States.

Founded in 1869, Santa Ana is located in Southern California adjacent to the Santa Ana River, 10 miles (16 km) away from the California coast. The city is part of the Los Angeles–Long Beach–Santa Ana metropolitan area which, according to the U.S. Census Bureau, is the second largest metropolitan area in the U.S., with almost thirteen million people. According to the 2000 U.S. Census, of U.S. cities with more than 300,000 people, Santa Ana is the 4th-most densely populated behind only New York City, San Francisco, and Chicago, and slightly denser than Boston.

Santa Ana lends its name to the Santa Ana Freeway (I-5), which runs through the city. It also shares its name with the nearby Santa Ana Mountains, and the Santa Ana winds, which have historically fueled seasonal wildfires throughout Southern California. The current Office of Management and Budget (OMB) metropolitan designation for the Orange County Area is "Santa Ana-Anaheim-Irvine, CA".