The critically injured person was taken to Thames Hospital by helicopter.
Police advised motorists to avoid the area and seek alternative routes if possible, as the road will be blocked for some time while emergency services work to clear the scene.
The serious crash unit has been notified.
A St John Ambulance media spokeswoman said three patients were taken via ambulance to Tauranga Hospital in a moderate condition.
The person airlifted out was in a serious condition.
Waka Kotahi NZ Transport Agency says State Highway 2 is closed between Old Tauranga Rd and Athenree Rd.
Southbound vehicles should detour via Waihi Beach Rd, Wilson Rd onto Seaforth Rd, Emerton Rd, Steele Rd and Athenree Rd for SH2 - reverse if travelling northbound.
A Fire and Emergency NZ spokesman said four fire trucks were called to the scene.
That included two from Mayor View Volunteer Fire Brigade and two rescue fire trucks from Waihi and Katikati fire brigades.
