A police spokesman said they were called to the three car crash on Waimate Highway (SH1) near the intersection with Horsnells Rd at 4.19pm.
One person was killed in the crash.
One of the seriously injured occupants was airlifted to Dunedin Hospital and the other three were transported to Timaru Hospital.
SH1 was expected to be closed for several hours while the Serious Crash Unit investigates the cause of the crash.
Diversions remained in place at the intersections of Barnetts Road/SH1 and Horsnells Rd/SH1.
In a separate crash in Northland, a female died after a collision just north of Towai.
Two other people are being treated for moderate injuries.
Sergeant Daniel Cleaver said the crash was near a sharp bend just north of the Towai Tavern.
Traffic was to be detoured onto Akarama Rd then Ruapekapeka Rd.
The diversion was only suitable for cars and light vehicles only. All heavy traffic was to be stopped and would have to wait on the side of the road.
The crash involved multiple vehicles.
At this stage the only available diversion for heavy vehicles is taking the alternate State Highway 15 route from Kaikohe or Whangarei.
The Serious Crash Unit is attending the incident.
A person at the Towai Tavern said he could not quite see the accident as it was just around the corner.