A man and a woman have been taken to Canberra Hospital in a critical condition after a serious crash at William Hovell Drive on October 12.
Only the drivers were in each car at the time of the collision, which took place about 7.30am.
ACT police said the two cars, a red sedan and a white SUV, collided head on.
Officer in charge of road policing Marcus Boorman said the car travelling in the northbound lane crossed over to the wrong side of the road before the collision.
It took emergency crews more than 90 minutes to cut both drivers out of their vehicles.
Both drivers sustained serious injuries as a result of the collision and were taken by ambulance to Canberra Hospital.
Detective Inspector Boorman described the scene as traumatic.
"They were very significant injuries," he said.
"When you look at any collision involving speed, it is a 90km/h speed zone here, the injuries become very severe."
A helicopter was considered at one stage to transport the drivers due to the severity of the crash.
William Hovell Drive remains closed between Coppins Crossing Road and Drake-Brockman Drive.
Crash investigators remained at the scene for several hours.
The road reopened to motorists after midday.
Detective Inspector Boorman said due to the nature of the collision, the investigation would take some time.
"It's a complex and time-consuming process," he said.
"From all accounts, it was a normal day on Canberra roads [until the collision happened]."
Police said there were multiple cars on the stretch of road at the time of the collision, and officers had already spoken to several witnesses.
ACT police said on Monday afternoon they were looking to speak to the driver of a black four-wheel drive that was travelling on William Hovell Drive at the time of the incident and narrowly avoided the collision.
Sergeant Stephen Booth said that driver was travelling in the southbound lane and had to swerve off the road to avoid the car travelling north who had crossed over to the wrong side of the road.
"We're hoping the driver might shed some light on the circumstances," Sergeant Booth said.
"There's no indication that driver has done anything wrong.
"A number of witnesses have already been in touch with us."
Anyone who saw the collision has been urged to contact ACT police.