Footage on Chinese state media showed damaged cars crushed under trucks, in which motorists became trapped and had to be rescued by firefighters.
Emergency services scrambled to douse in water a smashed-up lorry carrying hydrochloric acid, while 28 fire engines and 65 firefighters were dispatched to clear up the chaos.
In total, 16 separate accidents were reported, leaving nearly a thousand vehicles stranded.
It happened on a section of the Beijing-Hong Kong-Macau expressway, in the city of Zhumadian in Henan province.
Thick fog had covered the whole region before the deadly pile-up.
News agency Xinhua reported that everyone has now been rescued, the injured sent to a nearby hospital, and all traffic resumed.