The shooting in Fort Myers took place just after 12:30 a.m. (0430 GMT) in the parking lot of Club Blu, where officers found "several victims suffering from gunshot wounds," the Fort Myers Police Department said in a statement.
Between 14 and 16 people were wounded, with their injuries ranging from minor to life-threatening, according to police. A local hospital said victims were between 12 and 27 years old.
Police said three people had been detained for questioning and that the area was deemed safe, although roads in the vicinity remained closed. Investigators had yet to determine a motive and were seeking the identities of the two people who were killed, the statement said.
The shooting came six weeks after a massacre at a nightclub in the Florida city of Orlando, where a lone gunman who sympathized with Islamist extremist groups killed 49 people in the deadliest mass shooting in U.S. history.
About 150 miles southwest of Orlando in the Gulf Coast city of Fort Myers, Club Blu was hosting a "swimsuit glow party" for people all ages, according to a flyer posted on Twitter by local television station WINK. To enter, patrons were not required to show proof that they were the legal drinking age.
"It was a young teen event," Tatianna Nouhaioi, who was at the club, told ABC News. "There were kids. The kid I was holding in my lap, he was 14 years old that got shot."
Cheryl Garn, a spokeswoman for Lee Memorial Hospital in Fort Myers, said victims arriving there were as young as 12 years old. One of them died at the hospital, she said in a statement, while three others were admitted, one of them in critical condition and one in serious condition.
Police said shots were also fired at a nearby residence, where there was one minor injury.
Fort Myers police and the Lee County's Sheriff's Office were canvassing the area for other people who may have been involved, the statement said.
Representatives of the law enforcement agencies could not immediately be reached for further comment.
(Reporting by Frank McGurty; Writing by Mary Milliken; Editing by Catherine Evans and Lisa Von Ahn)