The Emilia Romagna Grand Prix in Imola was cancelled on Wednesday by Formula One and local organisers due to severe rain and floods in the northern Italian area.
The tournament could not be staged safely this weekend, according to the sport, and the decision was "the right and responsible thing to do given the situation confronting the towns and cities in the region."
There is limited room for rescheduling on a calendar that started with a record 24 events, dropped to 23 in January when China was cancelled, and is now due to close with 22.
On Monday, Italy's civil protection service issued a red alert weather warning for the area, and Transport Minister Matteo Salvini urged for the race to be postponed "to concentrate all efforts on coping with the emergency" on Wednesday.
Last year's event drew 129,000 spectators on Saturday and 64,000 on Sunday.
The Santerno river runs beside the Imola track, and while the paddock remained dry, water levels were increasing and adjacent areas, including car parks and several access roads, were flooded.
Stefano Domenicali, who was born in Imola and worked at the circuit as a child before joining Ferrari, said the decision not to proceed was justified.
"We need to ensure safety while not adding to the burden on the authorities as they deal with this terrible situation," he added.
The event was to be the season's sixth round and the first in Europe.
Ferrari, like with other drivers and teams, backed the cancellation.
"Even though it's our home race and therefore even more important to us, the main priority at the moment has to be the safety of all those living and working in the affected areas," the Italian team said in a statement.
Principal Fred Vasseur described the situation as "heartbreaking" to see.
Lewis Hamilton, Mercedes' seven-time world champion, told followers on social media, "We wish we could be racing, but this is definitely the right decision."
The Formula One team was asked to vacate the track on Tuesday due to water concerns. On Wednesday, the paddock remained closed.
The cars weren't supposed to hit the circuit until Friday, but the advance crew and technical specialists had already arrived to set up the garages and hospitality.
The Grand Prix was supposed to be the season's first triple header, with Monaco and Spain following on consecutive weekends.
Red Bull has won every race so far, and twice world champion Max Verstappen leads teammate Sergio Perez by 14 points.
"We agree with the decision. "The safety of all those involved and in the region is paramount and must take precedence," the squad wrote on Twitter.