A police officer at the scene of the crash has said that the road will be closed for a "considerable amount of time due to the complex nature of the incident."
North Yorkshire Police, North Yorkshire Fire and Rescue Service and Yorkshire Ambulance are currently at the scene of the crash which occurred at 10.55am
The A64 is currently closed between between Malton and Rillington and police are asking motorists to avoid the area using the A169 and A170 via Pickering.
In an online video, Inspector Paul Cording said that emergency services "are dealing with it as expeditiously as possible but due to the complex nature of the incident the road will be closed for a considerable amount of time."
The incident is also causing disruption to to the 843 bus services to and from Scarborough.
In a tweet Coastliner said: "Service disruption: to the 843 services to and from Scarborough there's been a serious RTA on the A64 we are having to divert through Thornton-le-Dale to and from Scarborough we are unable to serve Rillington Scampson and West knapton until the road has reopened."