A man in a silver VW Polo was driving along the A166 towards Fridaythorpe on Saturday afternoon, Humberside Police said.
A 65-year-old man on a Kawasaki 636 ZX6R and a 64-year-old man on a Honda CBR 1000 were travelling in the opposite direction.
The crash happened at 3.40pm on the stretch of road between the junctions with Barf Lane and The Balk.
Garrowby Hill is the summit of Bishop Wilton Wold, the highest point of the Yorkshire Wolds. It is the subject of a 1998 painting by Yorkshire artist David Hockney.
The two men riding the motorbikes were killed. Their families have been informed and are receiving support.
The 32-year-old car driver is in hospital with serious injuries.
Anyone who may have witnessed the crash or any of the vehicles prior to the crash is asked to call police on 101, quoting log number 428 of August 3, 2019.