The area now known as Pinellas County was first inhabited by the Timucua, one of four tribes in Florida. The Timucuans cultivated cornfields, constructed substantial homes and were very involved in trading with the residents of the north. When explorer Panfilo de Narvaez landed on the Pinellas Peninsula in 1528, he met great resistance from the Timucuans, and he and his crew suffered the ravages of storms, hunger and exposure which decimated the exploring party. Only four men found their way back to settlements in Mexico. Over the next 300 years, various parties of explorers attempted to settle the area, with little success. In fact, it wasn't until 1823 that Count Odet Phillippe, a surgeon in Napoleon's army, became the first permanent settler in Pinellas County.

A steady stream of settlers moved to the area throughout the 1800s, including such notable families as the Taylors, McMullens, Wilcoxes and Belchers. It was 1886, when the Orange Belt Railroad was coming through the area that residents came together to give their community a name. It seemed that the railroad would only build a station if the stop had a name. Some residents wished to name the town after the daughter of a prominent resident Gideon Blitch - Luluville. But ultimately they chose to name their town Largo, after the town's large lake. (In an ironic twist, the lake which gave name to Largo was completely drained by the Cross Bayou Drainage District 50 years later). Others argue that Largo gained its name from the city of Largo, Scotland, where several of the area's settlers came from. Because of its central location and rich farmlands, Largo quickly became the center of the area's citrus industry, earning the title "Citrus City." Largo citrus was being shipped by the ton to eager customers in the North.

The town was officially incorporated in 1905, and in 1913 became the first town in Florida - and second in the nation - to adopt a town manager form of government. The town grew rapidly through the boom times of the 1920s, but was hit hard by a freeze in the latter part of the decade, and then by the Great Depression. Due to mounting debt, the City of Largo was contracted to its original 1905 boundaries and once again became the Town of Largo.