Research shows fat people are propelled further forward during a collision because of their additional soft tissue which prevents a seat belt from tightening immediately against the pelvis.
Scientists now believe car design may have to change to protect overweight drivers.
Analysis of US collision data found those who were most overweight - in the World Health Organisation obesity category III - were 80% more likely to die in an accident than drivers of a healthy weight.
Those in category II were 51% more likely to be killed in a crash, while the risk was even lower for those in category I, at 21%.
When broken down by gender, obese women were found to be at greater risk than men. Those in obesity category III were almost twice as likely to die on the road than their male counterparts, the scientists said.
Their analysis of more than 3,403 pairs of drivers also showed underweight men were more likely to die in a collision than motorists of a healthy weight.
The authors said: ''Findings from this study suggest that obese vehicle drivers are more likely to die from traffic collision-related injuries than non-obese occupants involved in the same collision.
''Education is needed to improve seat belt use among obese people.''
They added: ''The ability of passenger vehicles to protect overweight or obese occupants may have increasingly important public health implications, given the continuing obesity epidemic in the USA.
''It may be the case that passenger vehicles are well designed to protect normal weight vehicle occupants but are deficient in protecting overweight or obese occupants.''
Offering a possible explanation for their findings, they referred to collision research which showed how the bodies of fat drivers were flung further forwards during a car crash than those of other motorists.
They said: ''Obese cadavers had significantly more forward movement away from the vehicle seat before the seat belt engaged the pelvis owing to additional soft tissue that prevents the belt from fitting close to the pelvis when the cadavers were in the driving position.
''The additional forward motion by cadavers was seen for the abdomen and lower extremities.''
But they said obese drivers may be more likely to have underlying health problems which could put them at higher risk in a road accident.
The authors, from the University of California and the University of West Virginia, published their findings in the Emergency Medicine Journal.