Juan Ponce de León visited in 1513, sailing into Biscayne Bay. It is unknown whether he came ashore or made contact with the Indians. Pedro Menéndez de Avilés and his men made the first recorded landing 1566 while looking for Avilés' missing son, shipwrecked a year earlier. Spanish soldiers led by Father Francisco Villarreal built a short-lived Jesuit mission at the mouth of the Miami River a year later. The Tequesta Indians were left to fend themselves from diseases like smallpox. The Tequesta sent a couple of local chiefs to Havana, Cuba to ask if they could migrate there. The Cubans sent two ships to help them, but Spanish illnesses struck and most of the Indians died.

The first permanent European settlers arrived in the early 1800s, people who came from the Bahamas to hunt for treasure from the ships that ran aground on the treacherous Great Florida reef. Some accepted Spanish land offers along the Miami River and Seminole Indians began to migrate to the area at about the same time. Following the Spanish sale of Florida to the United States, the area was affected by the Second Seminole Indian war with most of the population of Miami killed or driven off.

After the Second Seminole War ended in 1842, William English re-established a plantation on the Miami River. He charted the village of Miami on the south bank of the Miami River and sold plots of land. In 1844, Miami became the county seat, and six years later a census reported that there were ninety-six residents in the area.

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 Miami began its rapid growth as people flocked to the "Freeze Proof" land.

During World War II, many military schools, supply, and communications facilities were established in the area. Rather than building large army bases to train the men needed to fight the war, the Army and Navy took over hotels for barracks, movie theaters for classrooms, and local beaches and golf courses for training purposes. Over five hundred thousand enlisted men and fifty thousand officers trained in South Florida during the war, many of whom returned to Miami, pushing the population up to almost half a million by 1950.