The island of Key Largo is an exposed, fossilized remnant of a coral reef formed during a period of higher sea level and then uncovered and eroded during a subsequent ice age. The highest elevation is a slight ridge forming the spine of the island, which rises to about 15 feet above seal level.

The island's substrate is called Key Largo limestone; in many places, fossilized corals and smooth, eroded limestone "caprock" are visible at the surface. Solution holes, which are pockets dissolved in the limestone by acidic rainwater, form shallow depressions in the land. The natural shoreline of the island is generally rocky. 

Key Largo's climate is tropical. Frost has never been recorded on the island. Key Largo enjoys close to 3,000 hours of sunshine annually.