A Sydney police chase turns deadly as a man dies after a car being followed by two officers crashes.

A man has died and another is in custody after the crash, which police have described as an “unbelievable tragedy”.

An internal investigation has been launched into officers’ involvement in a collision that left a 49-year-old man dead on Tuesday morning.

Police were keeping an eye on a 43-year-old man who they said was driving suspiciously at 4am near the Great Western Highway at St Marys, in Sydney’s west.

They lost sight of the man’s Holden sedan before finding him again after he took the Toyota hatchback with the 49-year-old inside.

The man in the Toyota was given first aid but later died.

Police located the driver of the other vehicle behind someone’s home after he allegedly fled the scene.

He was taken to Nepean Hospital and police expect to charge him once he undergoes drug and alcohol testing.

Assistant Commissioner Gavin Wood said the death was an “incredible tragedy”.

One person has died and police declared a critical incident on Tuesday after a crash in western Sydney led to the closure of a major highway (pictured)

“You have an innocent 49-year-old man going to work – he doesn’t come to work, he doesn’t go home, his family can’t see him,” he told reporters.

“So you talk about tragedies… the lives of this poor man, his family and friends were changed by this incident.”

Police were not officially involved in the pursuit, but kept an eye on the sedan after believing the driver was acting suspiciously.

But Mr Wood did not go into detail about how the driver was acting suspiciously in order to pique the officers’ interest.

He said the driver had been disqualified from driving and was “well known” to police.

The crash and its investigation will now be subject to independent review after being declared a critical incident.

The Holden then crashed into a silver Toyota Corolla hatchback (pictured), killing the driver.

This process follows incidents where a person has been killed or seriously injured in police-related circumstances.

“We have two young police officers doing their job, looking out for the community. They became suspicious and as a result they followed the vehicle,” Mr Wood said.

“Circumstances that raise suspicion will form part of this critical investigation.”