The man is the fourth person to die on ACT roads in 2021, and the second to die on the Monaro Highway this year, following the death of a motorcyclist at Michelago last Tuesday.

The collision involved a Honda sedan and a Toyota Corolla and occurred at 1.20am.

The 19-year-old driver of the Toyota died at the scene.

The other driver involved in the crash was taken to hospital.

Detective Inspector Donna Hofmeier said it was disappointing to see ACT's road toll rise so early in the year.

"Ideally we would love to have no road toll at all," she said.

"My message to the ACT public is to think when they are driving; be careful road users, slow down, respect the road and respect other drivers on the road."

It appears the Toyota Corolla vaulted the safety barrier, rolled over and hit a tree.

It is not known at this time what caused the crash, which appears to have involved two cars travelling south on a straight section of roadway at high speed.

Investigators were expected to remain on the scene for many hours, with protective screens called in around 4.30am to shield the body from public view.

In the early hours of Monday morning, crash investigators also called for light towers to be set up so as to better examine the scene.

The incident occurred about 400 metres south of the Tralee Street intersection with the Monaro Highway.

Both southbound lanes of the highway are expected to remain closed until around lunchtime on Monday.

Southbound traffic will be requested to divert from the highway at Tralee Street, Hume. Northbound traffic was unaffected.

A Canberran was also killed in a major crash in South Australia over the weekend.

The 23-year-old ACT man was driving a Ford utility that collided with a B-double truck on the Stuart Highway at Wirraminna, in northern South Australia, about 12.15pm on Saturday.