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The shores of Tampa Bay were home to the Weedon Island Culture and then the Safety Harbor Culture for thousands of years. These cultures relied heavily on Tampa Bay for food, and the waters were rich enough that they were one of the few Native American cultures that did not have to farm. The Tocobaga was likely the dominate chiefdom in the area when Spanish explorers arrived in the early 1500s, but there were likely smaller chiefdoms on the eastern side of the bay which were not well documented. The indigenous population had been decimated by disease and warfare by the late 1600s, and there were no permanent human settlements in the area for over a century. The United States took possession of Florida in 1821 and established Fort Brooke at the mouth of the Hillsborough River in 1824.

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