Four people were taken to Tokoroa Hospital, three with moderate injuries and one with minor injuries, a police spokeswoman said.
The crash happened just after midday 18km south Atiamuri, north of Ohakuri Rd on SH1.
"One car is down the ditch, the other car appears to be on the road," the spokeswoman said.
The road was clear by 2.30pm and police were heading to the hospital once the scene had been completely cleaned up.
Two fire crews attended the scene from Tokoroa and Taupo.
"No one was trapped so we assisted police with traffic control," said Northern Fire Communications shift manager Paul Radden.