Regional chief Eugenio Giani said a red weather alert demanded that people exercise "maximum care and attention" amid "intense and persistent rain".
Several dozen people were told to evacuate with the help of firefighters from low-lying villages and a floodplain near Pisa, according to the ANSA news agency.
Florence authorities ordered the Uffizi Galleries, the world-famous art museum, to close early, and the Duomo said it was also shutting.
The fire service published images of cars partially submerged in the town of Sesto Fiorentino, north of Florence, as Giani told residents to keep clear of ground floors and basements.
"My thoughts go to the populations affected by the bad weather that is hitting various areas of Italy, causing serious damage and difficulties to citizens," Prime Minister Giorgia Meloni posted on X.
The government would "guarantee all necessary support," she said.
More than 500 firefighters were working across Tuscany, the interior minister said, with more than 300 interventions either carried out or planned.
Bernardo Gozzini from the Tuscan weather service Consorzio Lamma told the Corriere della Sera that 60 millimetres (2.4 inches) of rain had fallen in the area around Sesto Fiorentino between 6am and noon.
"In Florence, in the month of March, we usually have 70 millimetres of total precipitation," Gozzini said.
"It is as if a month's worth of rain had fallen in six hours."
Floodgates opened
Schools, parks and cemeteries in Florence and nearby Prato were closed on Friday after an order on Thursday.
Giani said floodgates and expansion tanks had been opened to ease the pressure on the Arno, the river that runs through Florence and Pisa.
In Florence, the Arno swelled to its highest level in the early evening but didn't break its banks, Giani said. The river was expected to reach its maximum level in Pisa overnight.
Three people and their dog were hoisted to safety by helicopter in Gattaia, northeast of Florence.
Alessio Mantellassi, mayor of Empoli, a town west of Florence, said in a live post on Facebook that the situation "is worse than in 2019", when Empoli experienced devastating flooding.
"It's one of the hardest moments in recent history," he said.
In Pisa, army soldiers placed sandbags behind a barrier lining a swollen river.
Pisa's Mayor Michele Conti said the situation was "very complex" and urged residents to stay home.
The northeastern Emilia Romagna region, where devastating floods left 17 people dead two years ago, was also under a red weather warning.
Some rivers in the region were already swollen by previous downpours.
Emilia Romagna President Michele De Pascale said there had been "very violent" weather on Friday morning.
"We must pay great attention, it is a basin that has been hit several times in recent years by floods," he said in a statement.
Scientists have warned in recent years that man-made climate change amplifies the risk of natural disasters such as floods.
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