Long before the park was established, the subtropical climate, clear waters and abundance of marine life attracted explorers. The Calusa Indians lived off the plant and marine life before the arrival of the first Spanish settlers. After Spanish occupation, other travelers from nearby islands such as the Bahamas made their way to Long Key.

By 1912, the Florida Keys were no longer considered a remote area to travel. By this time, the Key West Extension of the Florida East Coast Railroad was completed, allowing Long Key to become an important depot. Henry Flagler, the founder of the railroad, also established the Long Key Fishing Club which was a Mecca for the world’s greatest saltwater fishermen. This productive era came to a temporary end when a hurricane destroyed the railroad and fishing club in 1935.