Emergency services remain at the scene on the A64 at Copmanthorpe, York.
The force said: "The incident happened at around 1.10pm on the slip road towards Leeds and involved an articulated lorry and a car.
"A man has been airlifted to Leeds General Infirmary with injuries believed to be serious but not life threatening.
"A number of other people have been taken to York Hospital by road ambulance with serious but not life threatening injuries."
The road remains closed and police are urging drivers to avoid the area if possible.
North Yorkshire Fire and Rescue service also attended along with the Yorkshire Ambulance service and Air Ambulance.
They received a call at 1.13pm and four fire crews from York, Acomb, Huntington and Tadcaster have attended the incident.
Highways England said: "Due to necessary closures traffic is building up in the area and we are liaising with police. Further updates to follow"
Anyone who witnessed the incident is asked to contact police on 101, quoting the number 0221 of 30 April.