Ocala is located near what is thought to have been the site of Ocale or Ocali, a major Timucua village and chiefdom recorded in the 16th century. The modern city takes its name from the historical village, the name of which is believed to mean "Big Hammock" in the Timucua language. The Spaniard Hernando de Soto's expedition recorded Ocale in 1539 during his exploration through what is today the southeastern United States. Ocale is not mentioned in later Spanish accounts; it appears to have been abandoned in the wake of de Soto's attack.^{[citation needed]}

In the late eighteenth and early nineteenth centuries, Creek people and other Native Americans, and free and fugitive African Americans sought refuge in Florida. The Seminole people formed. After foreign colonial rule shifted between Spain and Great Britain and back again, in 1821 the United States acquired the territory of Florida. After warfare to the north, in 1827 the U.S. Army built Fort King near the present site of Ocala as a buffer between the Seminole, who had long occupied the area, and white settlers moving into the region. The fort was an important base during the Second Seminole War and later served in 1844 as the first courthouse for Marion County.^{[citation needed]}

The modern city of Ocala, which was established in 1849, developed around the fort site. Greater Ocala is known as the "Kingdom of the Sun".Plantations and other agricultural development dependent on slave labor were prevalent in the region. Ocala was an important center of citrus production until the Great Freeze of 1894–1895.^{[citation needed]}

Rail service reached Ocala in June 1881, encouraging economic development with greater access to markets for produce. Two years later, much of the Ocala downtown area was destroyed by fire on Thanksgiving Day, 1883. The city encouraged rebuilding with brick, granite and steel rather than lumber. By 1888, Ocala was known statewide as "The Brick City".^{[citation needed]}

In December 1890, the Farmers' Alliance and Industrial Union, a forerunner of the Populist Party, held its national convention in Ocala. At the convention, the Alliance adopted a platform that would become known as the "Ocala Demands". This platform included abolition of national banks, promoting low-interest government loans, free and unlimited coinage of silver, reclamation of excess railroad lands by the government, a graduated income tax, and direct election of United States senators. Most of the "Ocala Demands" were to become part of the Populist Party platform.^{[citation needed]}

The first thoroughbred horse farm in Florida was developed in Marion County in 1943 by Carl G. Rose. Other farms were developed, making Ocala the center of a horse-breeding area. Local horses have won individual races of the Triple Crown series; in 1978, Affirmed, who was bred and trained in Marion County, won all three races, boosting interest in the industry there.

Ocala is one of only five cities (four in the US and one in France) permitted under Chamber of Commerce guidelines to use the title, "Horse Capital of the World", based on annual revenue produced by the horse industry. 44,000 jobs are sustained by breeding, training, and related support of the equine industry, which generates over $2.2 billion in annual revenue. Postime Farms and Ocala serve as host to one of the largest horse shows in the country: H.I.T.S or "Horses in the Sun", a Dressage/Jumper event lasting about two months. It generates some 6 to 7 million dollars for the local Marion County economy each year. The show features classes for over 100 different breeds, including Tennessee Walker, Paso Fino, Morgan horse, Saddlebred, Draft horse and the American Quarter Horse. Other equine events in the area include mounted shooting by the Florida Outlaws, as well as endurance rides, barrel races, extreme cowboy events, jumper shows, trick shows, parades, draft pulls, rodeo events and more.

In the last decades of the twentieth century, the greater Ocala area had one of the highest growth rates in the country for a city its size. The population of Marion County in 2000 was more than 250,000, up from under 100,000 in 1975.

Many historic homes are preserved in Ocala's large residential Historic District, designated in 1984. East Fort King Street features many excellent examples of Victorian architecture. Ocala structures listed on the National Register of Historic Places include the Coca-Cola Building, the E. C. Smith House, East Hall, the Marion Hotel, Mount Zion A.M.E. Church, the Ritz Historic Inn, and Union Train Station.

The original Fort King site was designated as a National Historic Landmark in 2004.

As of the 2010 through 2014 census, Ocala was 63.3% non Hispanic white, 20.4% African American, 11.7% Hispanic or Latino, 2.6% Asian, 2% all other. As of the census of 2000, there were 45,943 people, 18,646 households, and 11,280 families residing in the city. The population density was 1,189.2 per square mile (459.2/km²). There were 20,501 housing units at an average density of 530.7 per square mile (204.9/km²). The racial makeup of the city was 72.9% White, 22.1% African American, 0.4% Native American, 1.2% Asian, <0.1% Pacific Islander, 1.8% from other races, and 1.6% from two or more races. Hispanic or Latino of any race were 5.7% of the population.

There were 18,646 households. 40.9% were married couples living together, 15.9% had a female householder with no husband present, and 39.5% were non-families. 33.0% of all households were made up of individuals, and 15.0% had someone living alone who was 65 years of age or older. The average household size was 2.29 and the average family size was 2.91.

In the city the population was spread out, with 23.2% under the age of 18, 9.3% from 18 to 24, 26.2% from 25 to 44, 20.9% from 45 to 64, and 20.4% who were 65 years of age or older. The median age was 39 years. For every 100 females, there were 89.7 males. For every 100 females age 18 and over, there were 85.5 males.