All the casualties were taken to hospital, two by air ambulance. Police were at the scene to carry out an investigation into the circumstances.
The southbound carriageway is closed between junctions 16 and 18, Holmes Chapel, and is likely remain closed for approximately four hours, police said.
"Crews were called to the scene of a major road traffic collision on the M6 southbound between junctions 17 and 16.
"There were seven service appliances at the scene which involved numerous vehicles including two heavy goods vehicles, two cars and one van. The crews were engaged in extricating five casualties who were trapped.
"The officer at the scene summarised that a total of 15 persons and nine vehicles were involved in the collision.
"Five persons were released from vehicles by the Fire and Rescue Service and all casualties were transported to hospitals at Leighton, Crewe and Stoke by the ambulance service. Sadly, one person was confirmed dead at the scene."