According to historians, it is believed that the name "St. Lucie" was first given to this area by the Spanish. The name was given after the Spanish began constructing a fort on December 13, the Roman Catholic Saint Lucia's feast day.

The "Santa Lucia" colony was established between Vero Beach and Stuart around 1567. Old Spanish maps identify this area as Santa Lucia, which included roughly what is now known as Vero Beach to Stuart. The Spanish held Florida from 1783 to 1819. Seminoles (Creek Indians from Alabama and Georgia) and runaway slaves began to settle on the Treasure Coast. The Anglo-Saxon version, "St. Lucie," would not be officially used to identify the area until the 1900s.