A British trading post called "Cottonton" was founded at this site on the mouth of the Apalachicola River.

Gradually, after acquisition by the United States and related development in Alabama and Georgia, it attracted more permanent European-American residents.

[2][3][4] Trinity Episcopal Church was incorporated by an act of the Legislative Council of the Territory of Florida on February 11, 1837.

In 1849, Apalachicola physician John Gorrie discovered the cold-air process of refrigeration and patented an ice machine in 1850.

[14] His patent laid the groundwork for development of modern refrigeration and air conditioning, making Florida and the South more livable year-round.

Before railroads reached the region in the later 19th century, Apalachicola was the third-busiest port on the Gulf of Mexico (behind New Orleans and Mobile).

[14] Scheduled boats transported passengers and goods up and down the Apalachicola, Chattahoochee, and Flint rivers to Albany and Columbus, Georgia.

A paddle steamer, the Crescent City, made a daily round trip to Carrabelle, carrying the mail as well as passengers and freight.

Originally built in 1935 and rebuilt in 1988, the John Gorrie Memorial Bridge carries U.S. 98 across Apalachicola Bay to Eastpoint.

U.S. 98 is the main highway through town, leading east across the bay to Eastpoint and northwest 59 miles (95 km) to Panama City.

Apalachicola is still the home port for a variety of seafood workers, including recreational fishing and shrimpers.

Today the oyster industry has completely collapsed due to pollution and lack of water flow in the Apalachicola River.

In 1979, Exxon relocated their experimental subsea production system from offshore Louisiana to a permitted artificial reef site off Apalachicola.

[25] Apalachicola is home to the Dixie Theatre,[26] a professional Equity theater which is also a live performance venue.