The collision, which involved six vehicles, happened shortly after 1am this morning at the entrance to the underpass on Lee Bank Middleway near Edgbaston in Birmingham.
West Midlands Police detectives have described the circumstances of the "serious collision" as "very difficult and upsetting."
Three men were killed after being thrown out of their car, while a black cab driver and his two passengers also died. Three other cars collided as they tried to avoid the initial crash.
Police are appealing for any witnesses to come forward.
Superintendent Sean Phillips said it was "way too early" to speculate on the reason for the crash.
He added: "It will take some time to unpick the scene and just understand exactly what's happened. It would be unfair for me to speculate at this time."
Supt Phillips said the speed of the vehicles and whether all those involved were wearing seatbelts would be looked at during the investigation.
The road had been gritted at 5pm the previous evening, he confirmed.
West Midlands Ambulance Service, which dispatched five ambulances and three paramedics, described the scene as "extensive and extremely complex."
Paramedics dealt with 13 patients in total.
A spokesman said a man and woman in the first car "astonishingly" escaped with "relatively minor injuries" despite extensive damage to their vehicle.
The black cab was discovered on its side and the ambulance service said "there was nothing that could be done to save the driver", who was confirmed dead at the scene.
Two passengers in the back, a man and a woman, were quickly removed by the emergency services. The woman was confirmed dead at the scene, while the man died in hospital.
Four men were travelling in the third car involved in the crash, and three of them were also confirmed dead at the crash site.
The other man has been taken to the major trauma centre at the Queen Elizabeth Hospital Birmingham, where he remains in a critical condition.
Of those travelling in the three other cars, two people were taken to Heartlands Hospital with minor injuries.
West Midlands Fire Service said 40 firefighters were sent to the "horrific" crash.