Three people have died in two separate road crashes near Katherine in the Top End and outside Yulara near Uluru, according to Northern Territory police.
The Stuart Highway was closed in both directions around 40 kilometres south of Katherine on Friday morning.
Police said local officers were on the scene and major crash detectives were also travelling from Darwin to respond.
No information about the cause of the crash or involvement of any other vehicles has been released.
The highway has reopened to smaller vehicles but police said delays are expected for several hours on Friday afternoon.
Police said officers also remain on the scene of an accident on the Lasseter Highway, about 15 kilometres outside Yulara.
A male passenger in his 30s was killed in what police said was a single-vehicle roll over that happened at around 4.00am.
In a statement police said the sedan rolled several times after it crashed, with the female driver and another female passenger left with non-life threatening injuries.
"Alcohol is believed to be involved and a sample of the driver's blood will be subject to forensic toxicology," Detective Senior Sergeant Brendan Lindner said.
