A Fire and Emergency New Zealand spokeswoman said crews from Mosgiel, St Kilda and Lookout Point stations were called to the scene on State Highway 1 near the Saddle Hill overpass about 3.30pm.
No-one was trapped, but fire crews assisted Hato Hone St John ambulance staff to treat four people with moderate to minor injuries, she said.
Police said the crash closed SH1 between the Quarry Rd Bridge and Saddle Hill overpass.
An Otago Daily Times reporter at the scene said a ute had knocked over part of the wire median strip in the centre of the road and stopped in the inner verge of the northbound lane.
A car lay further up the highway, across one southbound lane and the outer verge of the motorway.
Traffic heading south had backed up about half a kilometre and traffic in the northbound lane was down to one lane for a time, the reporter said.
Dozens of vehicles had parked up at the motorway lookout at the intersection of Coalstage Rd and Morris Rd to look at the scene.
At 6pm, police said the road was clear.
