Gov. Rick Scott said during a news conference in Orlanda that no mosquitoes in the state have tested positive for Zika. But he said one woman and three men in Miami-Dade and Broward counties likely contracted the virus through mosquito bites.
More than 1,650 Zika infections have been reported in the U.S., but the four patients in Florida would be the first not linked to travel outside the U.S. mainland.
Scott said health officials believe the infections occurred in a small area just north of downtown Miami.
Zika primarily spreads through bites from tropical mosquitoes. In most people, the virus causes only mild illness, but infection during pregnancy can lead to severe brain-related birth defects for the fetus.
Miami-Dade County has reported 96 Zika cases, the most in Florida so far, and Broward County has 55. Until Friday, health officials said all the cases stemmed from international travel.
Zika is mainly spread by mosquitoes, as well as sex. There is no vaccine.
The tropical mosquito that spreads Zika and other viruses is found in the southern U.S. While health officials have predicted that mosquitoes in the continental U.S. would begin spreading Zika this summer, they also have said they expect only isolated clusters of infections and not widespread outbreaks.
The U.S. Food and Drug Administration has told blood centers in Miami-Dade and Broward counties to suspend collections until they can screen each unit of blood for the Zika virus with authorized tests.
The FDA also has recommended that neighboring counties implement the same precautions, and visitors to South Florida in the last month are urged to defer donations as well.
The FDA previously advised U.S. blood banks to refuse donations from people who recently travelled to areas outside the country that have Zika outbreaks.
Florida's main supplier of blood, OneBlood, said it was working as quickly as possible to comply with the FDA's "unanticipated" request and would start testing all its collections for Zika on Friday.