Two trucks, one carrying dangerous substances, were involved in the smash with four cars just before midnight on Wednesday on the A9 motorway near Halle, Saxony-Anhalt. One of the cars burst into flames.
Both trucks turned over but neither lost any of their load in the accident.
At least 30 members of the emergency services helped the victims – but for one it was too late as they died at the scene of the crash.
The second fatality died in hospital and ten others were treated, broadcaster N24 reported on Thursday.
The A9 motorway, which runs between Berlin and Munich, was shut for several hours causing traffic jams down diversion routes.
As a knock-on effect from the accident, other motorways were busier than normal. On the nearby A14 between Halle and Magdeburg heavy traffic saw two minor crashes. One was with a truck and a car, leaving one person injured.
READ MORE: Mother and daughter die in Argentina bus smash