So far, cases outside of Latin America and the Caribbean, where the virus is prevalent, have been spread by travel to that region or sexual transmission.
The four Florida cases mean US mosquitoes may be carrying the virus.
Zika causes only a mild illness in most people but the virus has been linked to severe brain defects in newborns.
The Florida department of health said "a high likelihood exists that four cases are the result of local transmission", centred on one small area just north of downtown Miami.