This struggle, also known as the Billy Bowlegs War, was the final clash of an intermittent guerilla conflict between the Seminole Indians of Florida and the United States. It had started in 1817 with fierce Seminole resistance to land-coveting white settlers encroaching from neighboring Georgia, then resumed in 1835. The U.S. had adopted a policy of removing Indians to "Indian Territory" west of the Mississippi. By the mid-1850s, more than 3,000 Seminole had been deported.

The main remaining Seminole leader at this point was "Billy Bowlegs" (O-lac-to-mi-co), a chief who was part of a ruling family. In the 1850s, while he and fellow Seminole were still subsisting quietly on their own lands in south Florida, the chief was sorely provoked by a U.S. surveying corps under a Colonel Harney. Under cover of darkness, Harney and his surveyors sneaked into Bowlegs' flourishing banana plantation and thrashed the crop. When faced by the stunned chief, the surveyors bluntly claimed responsibility because they wanted "to see old Billy cut up." Thus began the Third Seminole War. Once again, the Seminole put up guerilla-style resistance.

Relentless U.S. military incursions, complete with bloodhounds, reduced the Seminole population to between 200 and 300. The war ended with Bowlegs' surrender on May 7, 1858. He had only 40 warriors with him. Shortly after, Colonel Loomis, commander of the forces in Florida, announced an end to all hostilities. In effect, the U.S. government had abandoned efforts to remove all Seminoles.

In exchange for small cash outlays, Bowlegs agreed to leave Florida with about 165 members of his tribe to Indian Territory in Oklahoma. The old chief died shortly thereafter. Two organized bands and several families stayed behind in Big Cypress and other secluded parts of Florida. The tiny remnant that hung on had never surrendered.