Six people in total have been airlifted to hospital after a tourist bus went off the road on the Te Anau-Mossburn Highway.
The incident happened on the Te Anau side of Gorge Hill at 8:10am, a police spokeswoman said.
"There were 17 passengers on the bus, including the driver and tour guide."
Ambulances and three rescue helicopters were dispatched, St John spokesperson Gerard Campbell said.
Four patients were airlifted to Dunedin Hospital, two with serious injuries and two with moderate injuries. Two patients with moderate injuries who were at the Fiordland Medical Centre are now being airlifted to Southland Hospital in Invercargill.
The rest of the passengers all received minor to moderate injuries and were taken by bus to the Fiordland Medical Centre, according to police.
The westbound lane on State Highway 94 is currently open under stop-go traffic management.
Police are investigating the cause of the crash and expect the road to fully reopen by 3:30pm.