The Tampa area was first explored by the Spanish in the 1500's but the first non-native settlement didn't happen until the US Army built Fort Brooke where today's Tampa Convention Center is in 1824. After that settlers started to build around the fort, looking for protection from the Seminoles. Previous to the European invasion, the Tocobaga inhabited a series of villages around the northern shores of Tampa Bay while the Calusa had villages around the bay's southern shores. Arrival of the Europeans brought diseases that almost wiped out the Calusa and Tocobaga. Expansion of the British colonies to the north pushed the Seminole south and as they flowed in, they assimilated the last of those two ancient tribes.

The Second Seminole War flared up in 1835 and many settlers in the area left. That war went on for almost seven years, finally ending with the Seminole pushed further inland and further south. Then the American settlers came back. Tampa incorporated as a village in 1849. Tampa was reincorporated as a town in 1855 but during the Civil War, the town's government ceased all functioning. Tampa Bay was blockaded by the Union Navy through most of the war and a few skirmishes were fought in the area. The war ended in April 1865 and Union troops occupied Tampa from May 1865 to August 1869. This was the time of a long-lasting yellow fever epidemic that effectively decimated the local population. In 1869, the citizens voted to disincorporate the town, then it was reincorporated in 1873. Phosphate (essential to the production of fertilizers) was discovered east of Tampa in 1883 and business picked up. The railroad arrived a bit later and with better shipping capabilities, the town started to really grow. Then Vicente Martinez Ybor moved his cigar factory from Key West to Ybor City (on the outskirts of Tampa in those days) in 1885. Tampa was reincorporated as a city in 1887.

In the 1890's, the first major resort construction began in the Tampa area. Henry Plant built the Tampa Bay Hotel, a 500+ room luxury resort among 150 acres of manicured gardens on the banks of the Hillsborough River. It was built in Moorish Revival style and is now part of the University of Tampa.

World War II saw a major increase in military activity around Tampa with the construction of MacDill Field (now MacDill Air Force Base) and a series of other military airports in the area. One of those former military airports is now Tampa International Airport and another is the St. Petersburg-Clearwater International Airport.

Tampa is home to the University of South Florida (ninth largest university in the US) and the University of Tampa. Other colleges and universities in the area include Argosy University, Everest University, Hillsborough Community College, Stetson University College of Law, The Art Institute, Strayer University, South University, Remington College, Ultimate Medical Academy, Southwest Florida College, Saint Leo University and the International Academy of Design & Technology.

With the boom in population in Florida beginning in the 1950's, Tampa has boomed, too. While the city itself still has a population of less than 400,000, the Tampa-St. Petersburg-Clearwater Metropolitan Statistical Area has 2.7 million residents and Greater Tampa Bay (which includes Bradenton and Sarasota to the south) more than 4 million residents.

Forbes Magazine ranked Tampa as the 5th best outdoor city in America in 2008. Loughborough University (England) ranks opportunity and quality of life in Tampa in the same ballpark as Osaka, Cologne and Phoenix.

Tampa is home to the Tampa Bay Lightning of the National Hockey League and the Tampa Bay Buccaneers of the National Football League. The Tampa Bay Rays play baseball across the bay at Tropicana Field in St. Petersburg.

Between 2000 and 2010, the population of Tampa rose more than 10%.