Two other people were flown to hospital with serious injuries.
Another serious crash on State Highway 2 near Wairoa at 1.05pm on Monday left one person with serious injuries.
A police spokeswoman said one person appeared to have sustained serious injuries follwing the crash involving a car and a truck near Cricklewood Rd and Poututu Station Road in Wairoa.
The spokesperson said traffic managment is still in place on State Highway 2 as of 4.40pm.
A St John spokesperson said they were notified of a motor vehicle incident at 1.10pm outside of Wairoa and responded with two ambulances and one helicopter sent to the scene.
St John assessed and treated one patient with serious injuries, who was then transported to Hawke's Bay hospital via helicopter.
A St John spokesperson said they were notified of a motor vehicle incident in Tarawera at 11.44am. Three ambulances and two helicopters responded.
They assessed and treated two patients with serious injuries, who were both transported by helicopter - one to Waikato hospital and one to Hawke's Bay hospital.
Lowe Corporation Hawke's Bay Rescue Helicopter Service general manager Ian Wilmot said the seriously injured person flown to Hawke's Bay Hospital was a man who appeared to be in his forties and was in a relatively stable condition.
Waka Kotahi confirmed the road closure on its website about 12pm.
"Due to a crash, State Highway 5 is closed between Taupō and Eskdale. Please avoid the area or consider delaying your journey," a note on the Waka Kotahi website reads.
A police spokeswoman said the incident happened about 11.45am.
A statement from the police said initial indications are that three vehicles are involved and the Serious Crash Unit has been advised.
Police are asking motorists to delay travel and avoid the area if possible.
Wilmot said one of his helicopters had attended the scene and one helicopter from Hamilton had also attended.
Matt Broderick, road policing manager for Eastern District Police, said most fatal incidents came down to several common factors, including speed, distraction, impairment and not wearing seatbelts.
"Distraction could be anything from the kids screaming in the car to somebody using a cellphone or mobile device," Broderick said.
"We are still finding up to 60 percent of the people that are involved in these crashes involve some sort of impairment, which could also be fatigue."
"If you're going to be in an accident, you want to be wearing a restraint. About 30 percent of people seem to forget that fact."
He suggests motorists always make sure they are fit enough to complete the drive and are alert and awake unencumbered by any alcohol or drugs, prescribed or otherwise.
Broderick said they should also pay attention to speed limits.
"A lot of our speed limits are not the most safe and appropriate speed and they are reviewing those, which is one of the reasons they changed the speed on State Highway 5 because the survivability of a mistake on that road is very poor."
He said the final important thing to do once in the car was to focus on the drive and avoid distractions.
The speed limit on a 76 kilometre stretch of State Highway 5 between Napier and Taupō was reduced from 100km/h to 80km/h in February of this year.