Police say the people in four cars that crashed on State Highway 1 near Sanson were wearing seatbelts and that's probably why they survived.
The crash initially blocked both lanes of the highway between Sanson and Bulls around 3pm Monday afternoon but one lane has since reopened.
One seriously injured person has been taken to hospital by helicopter.
Traffic is backed up and significant delays are expected.
Diversions remain in place at Fagan Road and Speedy Road.
As many as 15 people are reported to be injured in the pile-up.