Europeans and Seminole Indians began to settle southeast Florida at about the same time and by the time that Florida became the 27th State in the Union, there was a small settlement of about 70 people living on the New River near the current site of Fort Lauderdale. The justice of the peace for the community was William Cooley, who refused to prosecute two white settlers for the murder of a Seminole Indian, claiming lack of evidence. The Second Seminole Indian War started at this time and Cooley's family was killed during the war while he was away. This revenge killing prompted the other settlers in the area to leave, leaving the area to the soldiers and Indians.

During the War, a detachment of the Tennessee Volunteers led by Major William Lauderdale built a fort at the fork of the New River, giving the future city its name. Major Lauderdale and the Volunteers left shortly after it was built, and the fort was destroyed twice during the war, but each time it was rebuilt closer to the Atlantic Coast. After the war, southeast Florida remained a wilderness outside of Miami due to a lack of transportation.

In 1891, a wealthy Cleveland woman named Julia Tuttle purchased an enormous citrus plantation in the Miami area. She and William Brickell tried to get railroad magnate Henry Flagler to expand his rail line, the Florida East Coast Railroad, southward to the area, but he initially declined. Following the great Florida freezes of 1894 and 1895, which devastated most of the citrus industry in Florida, Flagler was persuaded to reconsider. Following the arrival of Flagler's railroad in 1896, the City of Fort Lauderdale began its rapid growth as people flocked to the "Freeze Proof" land.

In 1892 the Dade County government authorized a rock road to be built between Lantana and Lemon City, with an overnight camp and a ferry crossing established on the New River. A young Ohioan, Frank Stranahan, arrived to take charge of the facilities and soon established a flourishing trading post with the local Seminoles and by 1895 Stranahan’s Trading Post was a South Florida landmark. In 1896, the Florida East Coast Railway was extended south through Fort Lauderdale, providing rapid transportation from all parts of the nation to south Florida