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.
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.
The issue of masks has become highly politicised in the United States, with opponents saying having to wear them encroaches on personal freedom. There have been demonstrations against masks and other coronavirus measures in several states.
But on Saturday, President Donald Trump appeared wearing a mask in the public for the first time after previously casting doubt on their usefulness. He was visiting the Walter Reed military hospital outside Washington, where he met wounded soldiers and health care workers.
"I've never been against masks but I do believe they have a time and a place," he said as he left the White House.
The United States overall has been exceeding new daily totals of 60,000 cases for the past few days. Other states including Arizona, California and Texas continue to see a rising cases.
Since the pandemic hit the US, more than 134,000 people there have died with Covid-19.