Early Spanish explorers came into (sometimes violent) contact with the Tocobaga, whose principal town was at the northern end of Old Tampa Bay near today's Safety Harbor in Pinellas County, but the Tocobaga and their neighbors disappeared from the historical record by the early 1700s, as diseases brought by European explorers wiped out the local population and survivors were ousted by the raids and incursions of other tribes from the north, leaving the Tampa Bay area largely uninhabited for over a century.

People from Tampa have historically been called "Tampans", "Tampanians", or "Tampeños". According to local authorities, "Tampan" was formerly the most common, while "Tampanian" rose in popularity after the original term began to be used as an insult. "Tampeños" (or "Tampeñas" for females) generally refers to the mix of Cuban, Italian, and Spanish immigrants who began arriving in the late 1800s.

The Gasparilla Pirate Festival has been held annually since 1904. The theme of the festivities is an invasion by the mythical pirate José Gaspar (also known as Gasparilla). A popular figure in Florida folklore, he is said to have died by leaping from his ship rather than face capture by the U.S. Navy, leaving behind an enormous and as-yet undiscovered treasure.

Because Tampa Bay is only 12 feet deep on average, manmade shipping channels have been dredged to allow large ships safe passage to the Port of Tampa. The largest of these, the main shipping channel, is 43 feet deep and 40 miles long.

Although it is threatened by tropical storms and hurricanes almost every year, no hurricane has made landfall in the immediate Tampa Bay area since 1921 when one touched near Tarpon Springs and caused extensive damage throughout the region.

The Cuban sandwich is at the center of a long-running rivalry between Tampa and Miami, with various community leaders claiming to be home of the best. During a 2012 flare-up of the debate, the Tampa City Council voted to name the "Historic Tampa Cuban Sandwich" as the city's official "signature sandwich". A Tampa Cuban sandwich is distinct from other regional versions, as Genoa salami is layered in with the other ingredients, likely due to the influence of Italian immigrants living next to Cubans and Spaniards in the area.

Located south of Downtown Tampa, Bayshore Boulevard is the world's longest continuous sidewalk at 4.5 miles long. This gorgeous recreational path, used by cyclists, joggers, and walkers, is lined with palm trees and features never ending views of the bay.

The filming of Edward Scissorhands injected over $4 million into the Tampa Bay economy. Director Tim Burton filmed his goth classic all over the Tampa Bay area, but the majority of the production took place in the northern suburb of Lutz, where production designers found "a kind of generic, plain-wrap suburb", which they made to look almost like Monopoly pieces by repainting each of the houses in one of four colors: "sea-foam green, dirty flesh, butter, or dirty blue".

It is believed to mean "sticks of fire" in the language of the Calusa, an Indian tribe that once lived south of the area. This may relate to the high concentration of lightning strikes that the area receives every year during the summer months.

By 1880, the population of Tampa had dropped to about 700 residents, but the discovery of phosphate in the nearby Bone Valley region in 1883 was a major boon for the city. The mineral, vital for the production of fertilizers and other products, was soon being shipped from the Port of Tampa in great volume, and the once-struggling village of Tampa became a bustling boomtown almost overnight. By 1900, it had grown into one of the largest cities in Florida, and Tampa is still a major phosphate exporter.