It was incorporated in 1829 with an Intendant and four councilmen. It was finally named "Apalachicola" in 1831, and in 1882 became the county seat.

The Port of St. Joseph was established in 1836 to escape the control of the Apalachicola Land Company. The Lake Wimico and St. Joseph Canal Company was formed to build what became a railroad ( 1839) from Iola to St. Joseph to draw the cotton trade from the Apalachicola River.

This was Florida's first railroad. Florida's Constitutional Convention was held in St. Joseph in 1838. St. Joseph was not able to compete with Apalachicola, however, and major storms in 1837, 1839, and 1844, along with a yellow fever epidemic in 1841, destroyed the town.

Except for turpentine operations, St. Joseph was abandoned until the 1900 's . The area did not recover until the coming of the Port St. Joe Paper Company. A number of homes moved by barge from St. Joseph in 1844 are still standing in Apalachicola. It is estimated that 150 people lived in West Point in 1828 and 2,000 in 1838. However, the population would fluctuate according to trade and yellow fever conditions.

In 1835, during the fever months, August 1 to November 1, the Apalachicola Advertiser estimated that there were no more than seventy people in town. Cotton was shipped from December through June, with most of it shipped from January through March. In 1836, 50,000 bales of cotton were shipped from Apalachicola. It became the third largest cotton port on the Gulf Coast, ranking after New Orleans and Mobile. Some 1S steamboats, on the average, plied the river to Columbus, Georgia. Cotton would be shipped down river, compressed at some 43 cotton warehouses in town, and taken across the shallow bay by lighter to three-masted sailing vessels off West Pass between St. Vincent and St. George Islands.

These vessels would go to New England, England, France, Belgium, or wherever there were cotton mills or lace manufacturing centers. They tended to sail a triangular route among Boston or New York, Apalachicola, and Liverpool or Le Havre. There were foreign consulates in Apalachicola. Goods were also shipped up river to towns and plantations.

Among the family names of the factors in the city were Orman, Raney, Porter and Chittenden from the Middle and New England states. Florida became a state in 1845.