Three ambulances and two managers responded to the incident and all patients were transported to Whakatāne Hospital.
Diversions were put in place at Mill Rd and SH30 and Huna Rd and SH30.
Motorists were told to expect delays and avoid the area if possible.
A spokesman for Fire and Emergency New Zealand said they were called at 1:38pm.
He said both vehicles had one person trapped inside and both were extricated. Fire responders left the scene at around 2:40pm.
He did not have information regarding any injuries sustained or the cause of the crash.
In a statement around 4.20pm, police said the road was clear following the serious crash.
Police thanked motorists for their patient while emergency services attended.