Lying on the eastern shores of Florida's Saint Joseph Bay off the Gulf of Mexico, Port St. Joe is about 122 nautical miles (193 kilometers or 120 miles by air) east-southeast Pensacola and about 236 nautical miles (347 kilometers or 216 miles by air) northwest of Tampa. In 2007, just over 3500 people called Port St. Joe home.

Founded in 1835, Port St. Joe was at one time the biggest town in Florida until its population of about six thousand people was decimated by yellow fever in 1841. Saint Joseph Bay is one of the best natural harbors on the shores of the Gulf of Mexico, even though no rivers flow into the harbor.

In 1838, Port St. Joe played host to Florida's first constitutional convention as the territory planned for Statehood. By 1841, Port St. Joe had been abandoned as its population fled the yellow fever epidemic. In 1843, the abandoned town was destroyed by the storm surge associated with a hurricane. For most of the 1800s, Port St. Joe continued to be an uninhabited ghost town. The only remains of old Port St. Joe are tombstones in the Yellow Fever Cemetery.

In the early 1900s, a new Port St. Joe was established about two miles north of the site of the original town. The Constitution Convention Museum State Park in Port St. Joe explains the town's role in Florida's early history.

Port St. Joe is on the Gulf Intracoastal Waterway, a canal with that is 3.6 meters (12 feet) deep and 38 meters (125 feet) wide. The canal is maintained by the United States' federal government and stretches from St. Marks, Florida, to Brownsville, Texas. The Gulf Intracoastal Waterway allows barges to move inland on major rivers (like the Mississippi, the Tombigbee, and the Apalachicola).

The Port St. Joe shipping channel is authorized by Congress to be 10.7 meters (35 feet) deep, and it connects Port St. Joe with the important Gulf of Mexico shipping lanes. The Port St. Joe and the industries located there are served by the Apalachicola Northern (AN) Railway and then to CSX Transportation at Chattahoochee, Florida. Port St. Joe is linked to the Nation's highway system through US Route 98, State Road 22, and State Road 71. It is also connected to Interstate 10 through State Road 71.

Facilities in Port St. Joe include a chemical plant and manufacturer, a barge-to-rail transloading terminal, and a dive-cruise ship builder. Historically, Port St. Joe has shipped cargoes including forest products, chemicals, and coal.

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