The earliest archaeological evidence of human use of the Terra Ceia Aquatic Preserve (TCAP) area dates to about 8,000 BC and was recovered from spoil dredged from Terra Ceia Bay. Subsequent aboriginal occupations produced shell middens and mounds dating from 500 BC to the late 1400s. Sixteenth century explorers, including Narvaez and Desoto, found the Tampa Bay region settled by the Tocobaga, Pooy, Uzita, Yagua and Neguarete Indians.

After the virtual extinction of the Florida natives by the mid-1700s, Creek Indians from Georgia and Alabama, who later became known as Seminoles, moved south into the state, and the Tampa Bay area saw limited use as their hunting territory. Even though most of their operations centered on Charlotte Harbor, Cuban fishermen also established seasonal, shoreline camps around Tampa Bay. Under the Armed Occupation Act of 1842, homesteaders began to claim the land in the area south of the Fort Brooke (Tampa). Arriving on April 12, 1843, by way of Tampa, Joseph and Julia (Madam Joe) Atzeroth, along with their daughter Eliza, established a claim on Terra Ceia Island, not far from the camp of Miguel Guerero, a Cuban fisherman after whom Miguel Bay is named. They were the first permanent settlers on Terra Ceia Island. By the 1880s farming was well established in the area. The majority of the uplands surrounding the TCAP were historically farmed for vegetable and citrus crops, and were later the birthplace of the Florida gladiolus flower industry.

In the late 1880s, pebble phosphate deposits were discovered in the Peace River, then later in Polk County. Phosphate shipment became a major economic focus and an incentive for construction of both railroad and port facilities. In 1966, Borden Chemical Company constructed the now defunct Piney Point phosphate plant. In 1969, a 40 foot deep channel was extended from the Tampa Bay shipping channel to Port Manatee. This channel separates the Terra Ceia and Cockroach Bay aquatic preserves.