West Yorkshire Police is advising drivers to seek alternative routes and approach "with caution" as there are expected to be significant delays.
It follows the accident just before 9am which saw a man arrested for drink-driving and two people rushed to hospital.
West Yorkshire Police said the cars involved were a purple Peugeot and a black Audi S5.
A man in his 60s and a woman in her 70s were taken to Leeds General Infirmary.
Yorkshire Ambulance Service sent three ambulances to the scene. The man's injuries were not known, but the woman was seriously injured.
People travelling to the Huddersfield Town Football match against Chelsea later this afternoon are advised to plan their journeys and leave enough travelling time.