The Estero Bay Estuary is bordered on the west by a chain of barrier islands, which include: Estero Island, Long Key, Lovers Key, Black Island, Big Hickory Island, and Little Hickory Island, from north to south respectively. Within the estuary are hundreds of islands, many with no upland area. Mangrove trees are by far the most dominant vegetation in the bay, although extensive seagrass beds are found within the shallow bays and sounds. The climate in the region is subtropical with the majority of rainfall from June to September. The estuary is not supplied with freshwater by any major river, but rather by a number of small rivers and creeks.

The Estero Bay Aquatic Preserve, comprising the northern half of Estero Bay, was dedicated in December 1966, as the state's first Aquatic Preserve. During the 1983 session of the Florida legislature, the southern half of Estero Bay down to the Lee County line was added. Estero Bay Aquatic Preserve is approximately 11,000 acres of submerged lands.