State Highway 5 was temporarily closed after a fatal crash in Rangitaiki near Taupō.
A police spokeswoman said the crash happened about 1.25pm on the Napier-Taupō Rd near Rangitaiki School and Matea Rd.
Police confirmed two people had died and another person is seriously injured.
The road is now open to one lane and under stop/go management, NZTA tweeted.
Motorists should avoid the area or expect significant delays, a police spokeswoman said.
A Hawke's Bay DHB spokeswoman confirmed that two people were airlifted to Hawke's Bay Hospital in critical condition. Both were woman, one in her 20s and another in her 50s.
The spokeswoman said they were potentially expecting more injured coming in from the scene.
A St John spokesman said earlier that two helicopters and two ambulances were at the scene.
A woman at the nearby hotel said a witness to the crash described it as a "head-on".
The woman said it appeared a car had drifted across the centre line into another vehicle, which was then hit by an oncoming truck.
The person who called emergency services was "definitely shaken up".
"The car was right in front of them. It just veered across the centre line."
The woman said it was a sad start to Christmas for all of those involved.
A Rangitaiki Tavern worker said occupants from a car who witnessed the crash rushed to their pub to use the phone to call emergency services.
The crash happened near the tavern and there was no mobile phone reception out there, she said.
The eyewitnesses had come in looking frantic, she said.
The worker was told by the occupants that the crash looked "extremely bad".
She could see the odd car still going past, but expected the road would be closed.
"There are quite a few trucks lined up."
It comes less than an hour after police reopened SH25a at Kopu after a fatal crash earlier today.