The accident happened at around 1-15am when a silver Volkswagen Golf travelling east along Whalley Road in the direction of the A59 was involved in a collision with a lorry.
The driver of the Golf, a 28-year-old man, was pronounced dead at the scene.
The road remains closed this morning which has caused chaos and traffic gridlock.
PS David Hurst of the Road Policing Unit said: “A man has sadly died as a result of this collision and an investigation is underway to establish the full circumstances surrounding the incident.
"I would appeal to anyone who may have witnessed the collision or who has any information that could assist with our investigation to contact us.”
Anyone with information can contact police on 101 quoting log 65 of 26th September.