The collision took place on the A61 near South Stainley between Ripon and Ripley at around 10.45am yesterday.
It involved a Honda CBR600F motorbike, a silver Volvo V40, a silver Peugeot 3008 and a white Mini Cooper.
The motorbike, which was carrying a rider anad a pillion passenger, had been travelling in the direction of Ripon
A North Yorkshire Police spokesman today said: "Very sadly a 33-year-old woman from Harrogate, who was riding the motorbike, died at the scene.
"The pillion passenger was taken to Harrogate District Hospital."
The road was closed until around 4.30pm to allow officers to carry out a full investigation of the scene.
Now police are appealing for anyone who saw the collision, or any of the vehicles involved prior to it, to contact them.
Call 101, select option 2 and ask to speak to TS Zoe Billings or email [email protected] to pass on information.
Please quote reference number 12170069304.