The accident happened at about 8.45am on the southbound carriageway close to the Linhay junction.
A Suzuki Alto hatchback was in collision with a Massey Ferguson tractor and trailer being driven in the same direction.
Both Devon air ambulances were called out as was a police helicopter.
The teenager, 14-year-old Daniel Lang, and the front seat passenger, 24-year-old Melissa Barnham, were pronounced dead at the scene. Both were from Plymouth.
The three injured people were airlifted to Derriford Hospital.
The driver, a 26-year-old Plymouth woman, sustained a broken arm.
A 45-year-old Liverpool man and a 17-year-old Plymouth youth received what were described as serious injuries and at the time of going to press were still being treated in hospital although their conditions were described as stable.
The tractor driver, a 17-year-old from the area, was unharmed.
After the crash emergency workers closed both carriageways and screened off the area where the Suzuki had spun round and become embedded in the central reservation.
Dozens of fire and ambulance staff fought to free the passengers and specialist crash investigators studied the scene to determine the cause.
The northbound carriageway was reopened after 1pm but the southbound side remained closed until 6pm.
Friends and family have spoken of their shock and grief following the incident.
In a brief statement Miss Barnham's parents said: 'We are devastated at the tragic loss of our beautiful daughter Melissa.
'We would appreciate the time to be left to grieve at this most difficult of times.'
Police are still keen to hear from witnesses. Anyone with relevant information is asked to contact PC Gary Pocock of the Newton Abbot Roads Policing Unit on 08452 777444 quoting log number 208 of April 13.
Information can also be given anonymously by calling Crimestoppers on 0800 555111.