The pile-up happened on the northbound carriageway between Junction 16, for Crewe, and Junction 17, for Sandbach, at around 5.15pm on Friday.
The teenager was a passenger in a Volkswagen Polo. She was taken to hospital with life-threatening injuries but died hours later.
The Polo driver and another passenger, both men in their 20s, remain in hospital with serious injuries. A HGV, Peugeot 107 and a BMW were also involved in the crash.
The HGV driver, a 27-year-old man from Rossendale, Lancashire, was arrested at the scene on suspicion of causing death by dangerous driving. He remained in custody on Saturday.
A Cheshire Constabulary spokesman said: "At around 5.15pm on Friday, December 2, officers were called to the M6 between junction 16 to junction 17 northbound at Sandbach following reports of a collision involving a HGV, a Volkswagen Polo, a Peugeot 107 and a BMW.
"A passenger in the Polo, a 19-year-old woman from Dudley, was taken to hospital with serious and life-threatening injuries but, despite best efforts of all involved, has since passed away.
"The driver and another passenger in the Polo, two men in their 20s, remain in hospital with serious injuries."