Eight vehicles were involved in a crash on State Highway One, in Wairakei, between Palmer Mill Rd and Oruanui Rd.
Between 10 to 15 people involved in the crash were taken to hospitals in Tokoroa, Taupo, and Waikato Hospital.
A report from the scene is that the most severe injury was to a motorcyclist, who has serious injuries.
A full assessment of the crash is still being made by police, however, initial reports are that a truck crashed into the back of a vehicle, then shunted a number of other vehicles.
It is understood one of those vehicles was pushed across the road into oncoming traffic.
Tow trucks are now removing damaged vehicles from the scene.
Local diversions are in place and the road is expected to remain shut for about another hour.
The serious crash Unit and the commercial vehicle safety team are investigating.