Tybee would play a significant role throughout Georgia and U.S. history, including the Revolutionary War when Tybee served as the staging area for French Admiral D'Estaing's ill fated 1779 "Siege of Savannah" when combined multinational forces attempted to defeat the British held Savannah.

During the War of 1812, the Tybee Island Lighthouse was used as a signal tower to warn Savannah of possible attack by the British. Though no such attack took place, a "Martello Tower" was constructed on Tybee to provide protection in guarding the Savannah River. On the western end of the island, an area known as a "lazaretto", a variation of an Italian word meaning 'hospital for the contagious', was established to quarantine slaves and other passengers who might be carrying diseases. Mass burial on Tybee would be the final port of call for many of those quarantined there.

By the outbreak of the American Civil War, Tybee would again play an important military role in U.S. history. First Confederates occupied the Island. In December of 1861, the Rebel forces would withdraw to Fort Pulaski under orders from Robert E. Lee to defend Savannah and the Savannah River. Union forces under the Command of Quincy Adams Gilmore took control of Tybee and began constructing cannon batteries on the west side of Tybee facing Fort Pulaski about one mile away.

On April 11th, 1862, those cannon batteries would fire a new weapon called "Rifled Cannon" at Fort Pulaski and change forever the way the world protected its coastal areas. Within 30 hours, the rifled guns had such a devastating effect on the brick fort that it was surrendered and all forts like Pulaski were considered obsolete.

After the Civil War, Tybee began to grow as a resort area for local Savannah residents who wanted to escape the heat of downtown for the cooling breezes of Tybee Island. There were very few year around residents before the 1870's but by the 1890's there were over 400 beach cottages and other buildings built for the "summer" residents.

In 1855, Fort Screven was ordered built on the North end of Tybee to provide a more modern system of seacoast defenses. Six poured concrete low profile gun batteries and a minefield were ordered for Tybee along with hundreds of other military buildings. Gun Batteries, such as Battery Garland would be named to honor America's war heroes. From 1897 to 1947, Fort Screven would be an integral part of America's Coastal Defense system. Troops would train and stand guard on Tybee through the Spanish American War of 1898, World War I, and World War II. In 1947, the Fort was closed and sold to the Town of Tybee and Tourism returned as a major part of Tybee's history.

In 1961, Battery Garland, the former gun battery and magazine for a 12 inch long-range gun, became the Tybee Island museum. Rooms which once stored six hundred pound projectiles and two hundred pound bags of gun powder, now hold the collections and exhibits of over four hundred years of Tybee Island history.