Destin is located on a peninsula separating the Gulf of Mexico from Choctawhatchee Bay. The peninsula was originally an island; hurricanes and sea level changes gradually connected the island to the mainland.

Destin is near several other cities in the region. The city of Fort Walton Beach, Florida is located to the east at the inlet of Santa Rosa Sound into Choctawhatchee Bay. North of Destin across the bay is Niceville, Florida, with the Mid-Bay Bridge linking the two by road. At further distance are Panama City (to the east) and Pensacola (to the west), each about 50 miles away.

At the western tip of the peninsula is East Pass (also known as Destin Pass), separating it from Santa Rosa Island to the west. East Pass is the only outlet of Choctawhatchee Bay into the Gulf of Mexico. Many sources claim that the pass was dug by hand, with an inrush of water widening it within hours. This appears to be inaccurate: the pass appears in early maps and surveys from Spanish, French, and English surveyors, such as Thomas Jefferys's 1775 map The Coast of West Florida and Louisiana. Frequent dredging is required to keep East Pass navigable.

A significant sandbar located in East Pass is a popular anchorage in the area. The entrance to Destin Harbor, a lagoon between the beaches and the main body of the western portion of the peninsula, is located just north of the East Pass jetty. The lagoon is formed by a sand spit named Holiday Isle; many condominiums have been built along the harbor since the 1970s.

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