The area of New Smyrna Beach has a checkered history. Back in 1768, a Scottish physician named Dr. Andrew Turnbull began what was most likely the single largest attempt at colonization of the New World by a single member of British royalty. He transplanted about 1,500 settlers to the area from all over the Mediterranean world to grow sugar cane, hemp and indigo and produce rum. Over the next several years Native American raids and insect-borne diseases decimated the colony. Add mistreatment of the colonists by Turnbull himself and in 1777, the remaining colonists marched north to St. Augustine and filed complaints with the British Governor of Florida. Shortly after that, Florida reverted to Spanish control and Turnbull left the area to live in Charleston, South Carolina.

The Seminoles did irregular raids on the area and that served to keep most of the European invaders out until after the Civil War. The town of New Smyrna was incorporated in 1887 with a population of 150. The Florida East Coast Railway arrived in 1892 and the population began to grow steadily after that.

During Prohibition, the area of New Smyrna Beach saw a lot of activity from local moonshiners and rum-runners operating out of the Bahamas. In 1947 the community annexed Coronado Beach and the whole became "New Smyrna Beach."

Since 2000, the population of New Smyrna Beach has risen by more than 12%.