Florida has registered a state record of 15,299 new coronavirus cases in 24 hours - around a quarter of all of the United States' daily infections.
The state, with just 7% of the US population, surpassed the previous daily record held by California.
Florida, which began lifting coronavirus restrictions in May, has proved vulnerable due to tourism and an elderly population.
Its figures eclipse the worst daily rates seen in New York in April.
Florida also registered an additional 45 deaths.
The state would rank fourth in the world for new cases if it were a country, according to a Reuters analysis. More than 40 hospitals in Florida say their intensive care facilities are at full capacity.
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The latest figures were released a day after Walt Disney World in Orlando, Florida reopened, but with safety measures including mask-wearing and widespread use of sanitiser.
The caseload in Florida has continued to rise despite Republican Governor Ron DeSantis ordering some bars to close again last month.
The top adviser on the White House coronavirus taskforce, Dr Anthony Fauci, had criticised lockdown easing in the state, saying the data on infections did not support the move. Mr DeSantis has also declined to make mask-wearing obligatory.