The flooding was the second highest in the city's history, and the mayor has put the blame on climate change, Sky News reported.
Officials said the tide peaked at 187 cm (6.14feet) at 10.50 p.m. (local time) on Tuesday, just short of the 194 cm seen in 1966.
The high water submerged the city's historic squares and alleyways, including some of the favourite tourist spots such as St Mark's Square.
A man in his 70s, died on the barrier island of Pellestrina after being electrocuted, and another person died on the same island, though the cause was unknown, the media report quoted Italian news agency ANSA and others.
Saint Mark's Basilica, parts of which date to the 11th century, was also flooded, with an official even pointing to a risk of collapse.
"We were on the verge of the apocalypse", said Pierpaolo Campostrini, a member of St Mark's Council.
"The water could have imperilled the columns that hold up the basilica," he was quoted by Italian newspaper Corriere della Sera.
Venice Mayor Luigi Brugnaro called for the state of emergency to be declared, and Italian Prime Minister Giuseppe Conte said he would visit the city to assess the damage first-hand.
Brugnaro said: "The situation is dramatic. We ask the government to help us. The cost will be high.
"This is the result of climate change. A high tide of 187 cm is going to leave an indelible wound."
( With inputs from IANS )