Santa Ana is the most populous city in Orange County and has an estimated population of 353,184. Among U.S. cities with more than 300,000 people, Santa Ana is the 4th-most densely populated. Santa Ana lends its name to the Santa Ana Freeway (Interstate 5), which runs through the city. It also shares its name with the nearby Santa Ana Mountains and the infamous Santa Ana Winds, which historically have fueled seasonal wildfires throughout Southern California.

Santa Ana is the corporate headquarters of several companies including First American Corporation, Ingram Micro, The Orange County Register, Greenwood & Hall, Behr Paint, and Wahoo's Fish Taco. It also houses major regional headquarters for the Xerox Corporation and T-Mobile.  One of Santa Ana's most notable businesses is the Rickenbacker musical instrument company, whose electric guitars and bass guitars earned fame in the hands of many rock and roll legends.