Claimed in 1869 by Kentuckian William H. Spurgeon on land obtained from the descendents of Jose Antonio Yorba, Santa Ana was incorporated as a city in 1886 with a population of 2000 and in 1889 became the seat of the newly formed Orange County.

By 1906 the Pacific Electric Railway from Los Angeles was extended to Santa Ana, running along Fourth Street downtown. The "red cars" made travel to Los Angeles easier and helped continue Santa Ana's population boom. Due to declining ridership, the route was abandoned by the 1950s and the tracks were removed along with much of the rest of the Pacific Electric system. The closing coincided with the opening of the Santa Ana Freeway in 1953, increasing the ease of travel by automobile.

Santa Ana was the home of the original Glenn L. Martin aviation company, founded in 1912 before merging with the Wright Company in 1916. Later, Glenn Luther Martin created a second company of the same name in Cleveland, Ohio which eventually merged with the Lockheed Corporation to form the largest defense contractor in the world, Lockheed Martin.

In 1987, MainPlace Mall (now Westfield MainPlace) was opened north of downtown and became a major retail center for the area.

In November 1988, Santa Ana became a charter city, which allowed citizens to directly vote in mayoral elections. The current mayor of Santa Ana is Miguel A. Pulido, the first mayor of Latino descent in the city's history.

Since the 1980s, Santa Ana has been characterized by an effort to revitalize the downtown area which had declined in influence. The Santa Ana Artist's Village was created around Cal State Fullerton's Grand Central Art Center to attract artists and young professionals to live-work lofts and new businesses. The process has continued into 2009 with the reopening of the historic Yost Theater.

According to the United States Census Bureau, the city has a total area of 27.5 square miles. 27.3 square miles of it is land and 0.2 square miles of it (0.90%) is water. It is the 4th most densely populated place in the United States with a population of 300,000 or more with 12,471.5 people per square mile.

Santa Ana is nested on flat, low-lying plains with little land elevation change. Running through the west end of the city is the mostly channelized Santa Ana River, which is also largely seasonal due to the construction of the Prado Dam and Seven Oaks Dam. The river has caused several severe floods in the 20th century, and is a continued threat despite the existence of the dams.

Now fully developed, Santa Ana has several distinct districts. The core of the city is the downtown area, which contains both retail and housing, as well as the Santa Ana Civic Center which is a dense campus of administrative buildings for both the city and the county of Orange. The civic center is also home to the Ronald Reagan Federal Building and Courthouse. Several historic homes dating from the late 1800s can be found as well, and their preservation is a key issue as development of the downtown area continues.

North of downtown is the "Midtown" district along Main St., home to entertainment destinations such as the Bowers Museum, MainPlace Mall, and the Discovery Science Center.

Near the intersection of the Santa Ana Freeway and the Costa Mesa Freeway is the newly-designated "Metro East" area, which the city council has envisioned as a secondary mixed-use development district. Currently the area is occupied by several office towers, but little retail or housing. Also on the east side of the city is the Santa Ana Zoo, notable for its collection of monkeys and species from South and Central America.

The south end of the city is part of the South Coast Metro area, which is shared with the city of Costa Mesa. South Coast Plaza, a major shopping center, is the primary destination of this area, which also contains several high-rise office and apartment buildings.

Santa Ana experiences a Mediterranean climate, with mild, wet winters and the dry, warm sunny weather that Southern California is famous for in summer. Winter daytime temperatures average in the high 70s to low 60s (degrees Fahrenheit), and summer daytime temperatures average in the low 80s to mid 90s. Rainfall averages about 14 inches per year, most of which falls from November to April. There are an average of 34 days with measurable precipitation annually.

Santa Ana Unified School District includes thirty-seven K–5 elementary schools, nine 6–8 intermediate schools, eight 9–12 high schools, five special schools, and one charter school. The school district provides an online accountability report card.

Santa Ana Unified School District's public high schools include Valley High School (Santa Ana), Middle College High School, Santa Ana High School, Saddleback High School, Century High School, newly opened Godinez Fundamental High School, Cesar E. Chavez High School, and other major schools in the area, along with the Orange County High School of the Arts in the midtown district.

The Roman Catholic Diocese operates Mater Dei High School. The Diocese also operates several K–8 schools in Santa Ana including: School of Our Lady, Saint Anne, Saint Barbara, and Saint Joseph. (Immaculate Heart Of Mary And Our Lady Of the Pillar schools were closed in 2005 and merged into the School of Our Lady which is located at Immaculate Heart of Mary Parish.

The city is home to Santa Ana College, a two year public community college, as well as California Coast University, and the Orange County branch of the Art Institute of California. Taft Law School a correspondence law school is also based in Santa Ana.

The 2010 United States Census reported that Santa Ana had a population of 324,528. The racial makeup of Santa Ana was 148,838 White, 4,856 African American, 3,260 Native American, 34,138 Asian, 976 Pacific Islander, 120,789 from other races, and 11,671 from two or more races. Hispanic or Latino of any race were 253,928 persons.

Breaking out the Hispanic and Latino population, the racial and ethnic composition of the population was 9.2% non-Hispanic white, 1.0% non-Hispanic black, 0.5% Hispanic black, 1.0% Native American, 7.1% Vietnamese, 3.4% other Asian, 0.2% Samoan, 0.1% other Pacific Islander, 0.1% non-Hispanic reporting some other race, 3.6% reporting two or more races and 78.2% Hispanic or Latino. A total of 71.0% of the population reported being Mexican.

As of 2007, there were 327,780 people, and 77,922 housing units. Santa Ana's property occupation density is 4.6 per housing unit, the highest of any American city over 50,000. (By contrast, New York's is 2.8, and Los Angeles's density is 2.6 persons per housing unit.)

The racial makeup of the city, as of 2007, is 42.6% White, 16.6% African American, 0.2% Native American, 9.4% Asian, 0.4% Pacific Islander, 46.3% from some other race, and 1.5% from two or more races. Hispanic and Latino Americans compose 64.1% of all residents; 63.1% are of Mexican descent.

As of the census of 2000, there are 337,977 people, 73,002 households, and 59,788 families residing in the city. (Owing to the large percentage of illegal immigrants in the Latino population in Southern California, this figure is widely believed to suffer from significant downward bias, and some estimates place the city's population at over 500,000.)

The population density is 12,451.9 per square mile. There are 74,588 housing units at an average density of 2,748.0 per square mile. The racial makeup of the city is 42.73% White, 1.70% African American, 1.19% Native American, 8.81% Asian, 0.34% Pacific Islander, 40.64% from other races, and 4.58% from two or more races. 76.07% of the population are Hispanic or Latino of any race.

There are 73,002 households out of which 53.2% have children under the age of 18 living with them, 60.6% are married couples living together, 13.5% have a female householder with no husband present, and 18.1% are non-families. 12.7% of all households are made up of individuals and 4.6% have someone living alone who is 65 years of age or older. The average household size is 4.55 and the average family size is 4.72.

In the city the population is spread out with 34.2% under the age of 18, 12.8% from 18 to 24, 34.1% from 25 to 44, 13.5% from 45 to 64, and 5.5% who are 65 years of age or older. The median age is 26 years. For every 100 females there are 107.7 males. For every 100 females age 18 and over, there are 108.7 males.

The median income for a household in the city is $43,412, and the median income for a family is $41,050. Males have a median income of $23,342 versus $21,637 for females. The per capita income for the city is $12,152. 19.8% of the population and 16.1% of families are below the poverty line. Out of the total population, 24.1% of those under the age of 18 and 10.4% of those 65 and older are living below the poverty line.

Santa Ana is the corporate headquarters of several companies including Behr Paint, CoreLogic, Corinthian Colleges, First American Corporation, Greenwood & Hall, Ingram Micro, The Orange County Register, Powerwave Technologies, SchoolsFirst Federal Credit Union, STEC, TTM Technologies, 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.

Then Glenn L. Martin Company, a precursor to Lockheed Martin, was founded in Santa Ana in 1912 before merging with the Wright Company in 1916.

In recent years, the nearby city of Irvine has outpaced Santa Ana in commercial growth, with the Irvine Business District located near John Wayne Airport. To compete with this, Santa Ana has approved commercial projects in the South Coast Metro area, as well as the "Metro East" development, located at the confluence of the Santa Ana Freeway and the Costa Mesa Freeway.

The Historic South Main Business District contains many older retail shops and other small businesses. It extends from downtown Santa Ana southwards on Main Street to the South Coast Metro area.

Amtrak, the national passenger rail system, provides service to Santa Ana several times on weekdays with less frequent service on weekends. It operates its Pacific Surfliner between San Diego to the south and either Los Angeles or Paso Robles to the north (see Santa Ana Regional Transportation Center). Greyhound USA is the largest bus transportation service in Santa Ana. Greyhound serves the continental United States and Canada. The bus lines Crucero, Intercalifornias, and others serve all points into Mexico.

Santa Ana is also served by Metrolink's Orange County Line (Oceanside to Union Station), and Inland Empire-Orange County Line (San Bernardino to San Juan Capistrano).

Santa Ana is in the preliminary stages of implementing a street car system that will connect the Santa Ana Train station to Downtown Santa Ana.

Public transit bus service is available via the Orange County Transportation Authority (OCTA).

John Wayne Airport is located at 18601 Airport Way Santa Ana, CA 92707. The IATA code for the airport is SNA.

Santa Ana is home to some of the most successful sports high school and collegiate sports teams in the nation. Mater Dei High School has one of the most successful and reputable American football programs in the country. The Dons of Santa Ana College are one of the most successful soccer teams in the state of California, and is a frequent top finisher, statewide. In 2008 the Dons clinched their fifteenth consecutive Orange Empire Conference title. The college is also known for its historically successful baseball teams.

Santa Ana has a number of parks that provide an improved quality of life for the residents. Disneyland and Knotts Berry Farm amusement parks are located northeast of Santa Ana, several kilometers away. Beaches are located around 20 minutes to the south, accessible by the 55 freeway. Huntington Beach and Newport Beach as well as other coastal communities offer world-class shopping, dining, boating, swimming and surfing opportunities.

• Artist Village and Civic Center (See Downtown Santa Ana Historic Districts).
• Bowers Museum - History museum started in the 1930s with a large collection of Central American artifacts.
• Heritage Museum of Orange County (formerly Centennial Heritage Museum) - home of the Kellogg House and other 1890s buildings
• CSUF Grand Central Art Center - At the heart of the Artist Village in Santa Ana.
• Delhi Park and El Salvador Park (Artesia Pilar Neighborhood)
• Discovery Science Center.
• Downtown National Register District.
• Downtown Santa Ana Historic Districts.
• Dr. Willella Howe-Waffle House and Medical Museum.
• El Centro Cultural de México.
• Galaxy Theatre.
• Historic Floral Park.
• Historic French Park.
• Main Place Mall opened in 1987.
• OC Pavilion performing arts center and 5-star restaurant Ambrosia.
• Old Orange County Courthouse.
• Santa Ana Civic Center.
• Santa Ana College, part of the Rancho Santiago Community College District.
• Santa Ana Fire Department's Firefighter's Museum.
• Santa Ana Historical Preservation Society.
• Santa Ana Zoo, built in 1960.
• Santiago Art District.
• St. Joseph Catholic Church, established in 1887, renovated in the late 1980s.
• Sol Art Gallery Cafe.

Greenville, a formerly rural section of Santa Ana, has buildings over a century old, but industrial complexes have replaced the agricultural fields that once surrounded the town.

Santa Ana has several wall paintings and murals depicting local history, community events and cultural diversity in Orange County.

• Riverview Golf Course
• Willowick Municipal Golf Course
• Pacific Electric Sub-Station Number 14
• Southern (D), Builders Exchange Building
• Ronald W Reagan Federal Courthouse
• Newhope Branch Santa Ana Public Library
• Dr. Willella Howe-Waffle House
• Bowers Museum of Cultural Art
• Santa Ana City Hall
• Santa Ana Public Library
• Santa Ana Regional Transportation Center
• McFadden Branch Santa Ana Public Learning Center
• Santora Building
• Heritage Museum of Orange County (Kellogg House)
• Old Orange County Courthouse
• Rankin Building
• Dexter's Chomp House