St. Marks was founded by the Spanish as San Marcos de Apalache, a fort built in the 1600's but destroyed by hurricanes and rebuilt several times until it came into US possession in 1821 with the rest of Florida. After the first couple destructions, the Spanish began quarrying limestone nearby and built the fort the final time in stone. It's part of that stone fort that survives today. The Spanish also built a tower beside their quarry and if they'd lit torches on the tower, it would have been the first lighthouse in Florida. The St. Marks Lighthouse itself wasn't built until 1830 and has also been rebuilt a couple times after sustaining damage from passing hurricanes.

The most famous incident happening at the fort seems to have occurred when Andrew Jackson invaded Spanish Florida in 1818. The Spanish had abandoned St. Marks and it was at the fort that Jackson executed two British nationals: Alexander Arbuthnot and Robert Christie Ambrister. They were accused (and apparently convicted) of inciting the local natives to attack American settlements further to the north in Alabama.

The town of St. Marks that we see today had its roots in a railroad terminus built on the harbor at St. Marks. The rail line was built around 1836 and served to transport cotton to the ocean for export up until the time of the Civil War. The railroad line today is a popular 16+ mile paved hike, bike and equestrian trail ending at the St. Marks waterfront. Other than the touristic attractions and some really good fishing, there isn't much here any more. That said, the population of St. Marks is up more than 7% since 2000.