In 1821, the United States acquired the territory of Florida from the Spanish and in 1824, the Armed Occupation Act allowed for private ownership of land along Sarasota Bay. The native Seminole Indians were not allowed to become citizens or own land and were pushed further south. In 1855, the settlers won their war with the Seminoles but it wasn't until the 1880's that development really began. William Whitaker is the first documented pioneer of European descent in what now is Sarasota, eventually starting a cattle ranch in 1847.

One of the earliest pioneer locations preserved in the Sarasota Bay area, is Historic Spanish Point, where the Webb family settled in 1867.They named the homestead "Spanish Point" in honor of the Spanish trader who had recommended the site to them. The 30 acre pioneer site has been listed on the National Register of Historic Places as Historic Spanish Point and is open to the public for a fee.

In 1885, Sarasota was heavily promoted in Scotland for its warm climate and bountiful land. Many families sailed to America expecting fields of vegetables, housing, and citrus groves. After a fluke snow storm, they found only a snow covered Main Street and many of the colonists left. John Hamilton Gillespie, a Scottish aristocrat, and member or the Queen's Bodyguard for Scotland, built what is believed to be America's first golf course in Sarasota. Gillespie also built the DeSoto Hotel on Main Street for tourists and prospective investors. In 1902, he was elected as Sarasota's first mayor. Sarasota has a strong Scottish influence to this day.

Sarasota's most notable attraction is the John and Mable Ringling Museum of Art, the state art museum for Florida, housed in the estate left to the state of Florida by John Ringling. The Ringling family moved to Sarasota in 1919 and made it the winter home of their famous Circus. During the following decades, the Ringling family were responsible for much of the development of Sarasota county, including the barrier islands. John Ringling was a partner in the company that built the first bridge to St. Armands Key and later he donated the bridge to the county.