Ocoee is located at 28°34′27″N 81°31′50″W / 28.574050°N 81.530596°W / 28.574050; -81.530596.

According to the United States Census Bureau, the city has a total area of 15.7 square miles (40.6 km), of which 14.7 square miles (38.1 km²) is land and 0.97 square miles (2.5 km) (6.12%) is water.

In the mid-1850s, Dr. J.D. Starke, stricken with malaria, took a group of slaves, similarly stricken, to the north side of an open pine wooded lake that provided clear and clean water to avoid further malaria outbreaks. The camp built by the group provided a base of operations from which to commute during the day to work the fields near Lake Apopka and rest at night. As the camp grew into a village, it took the name Starke Lake, a name the lake upon which the group settled bears to this day. The city's population increased further after the American Civil War as Confederate soldiers and their families settled into the area, including Captain Bluford Sims and General William Temple Withers who wintered at the location. Captain Sims received a land grant for a 74-acre parcel to the west of Starke Lake in what is now the downtown portion of Ocoee on October 5, 1883. In 1886, Captain Sims, along with a group of original settlers, led an effort to have the town platted and changed the name to Ocoee, after a river he grew up near in Tennessee. Ocoee is a Cherokee Indian word anglicized from uwagahi, meaning "apricot vine place" and this inspired the choice of the city's flower.

Bluford Sims began groundbreaking work in budding wild orange trees while in Ocoee. His commercial citrus nursery was the first in the United States in Ocoee, supplying many other groves in Florida with their first trees as well as shipping young citrus trees to California. The construction of the Florida Midland Railroad in the 1880s spurred growth in the area and many more settlers moved in.

On November 2, 1920, after July Perry and Mose Norman, two Black men, attempted to vote and encouraged other Black people to vote, the entire Black population of the town was attacked by a mob organized by the Ku Klux Klan. On the night of the massacre, white World War I veterans from throughout Orange County murdered dozens of African-American residents. At least 24 Black homes were burned, the institutions constituting the Black community were destroyed, and Perry was lynched. Before the massacre, Ocoee's Black population numbered approximately five hundred; after the massacre, however, the Black population was nearly eliminated. For more than 40 years, Ocoee remained an all-white sundown town. In 2018, the city commission issued a proclamation formally acknowledging the massacre and declaring that Ocoee is no longer a sundown town.

Ocoee was incorporated in 1922 (or 1923) and became a city in 1925.

Highway construction was the impetus for Ocoee's growth in the 20th century. State Road 50 (SR 50) was constructed south of downtown Ocoee in 1959 and provided a direct east-west connection between the City and a growing Orlando. The development of what would become Florida State Road 50 made the town more accessible to housing developers. Florida's Turnpike was opened just south of downtown Ocoee in 1964. In late 1990, Ocoee was connected to Orlando by a western extension of Florida State Road 408 (the East-West Expressway) which then joined the Florida's Turnpike south of SR 50. In 2000, the completion of Florida State Road 429 (the Western Expressway) linked Ocoee with Walt Disney World to the south.