Only half of the motorways in England reach the top safety rating, with other major roads much worse, a report says.
The study, which analysed motorways and major A-roads, says many do not protect drivers who run off the road.
The Road Safety Foundation says crashes cost £18bn a year and many roads could be improved relatively easily.
But the Highways Agency says England's roads are among the world's safest, saying it funds the study to help identify where to focus improvements.
The Road Safety Foundation - the UK arm of the European Road Assessment Programme (EuroRAP), the sister organisation of EuroNCAP which measures car safety - inspected virtually all of the 4,350 miles (7,000km) of motorways and major A-roads in England.
It then gave each a star rating from one to four - in much the same way as the car safety rating system works.
Only half of motorways were given four stars. Although they fared well on junction safety and head-on collisions, many did not protect users who ran off the road.
Unprotected signs and trees can turn a relatively minor problem with a tyre for example, into a fatal crash. There are 10 deaths a year on Britain's motorways caused by motorists hitting trees.
When the Foundation's German equivalent did its work, 70% of motorways there reached the four star standard - though not all the network was surveyed.
Most dual carriageways - 78% - were given three stars, with only 20% getting a four-star rating.
Most did well on head-on protection, but poorly for run-off protection. A quarter had junctions, lay-bys and minor accesses which were not considered suitable for a major road.
Single carriageway major A-roads fared the worst of all, with most getting only two stars. They lacked many of the safety features to protect drivers, including oncoming traffic often only being separated by a white line even when speeds were high.
"If a driver is belted, sober and obeying the speed limit, then the risk of death and injury in a four-star car on a four-star road is small," said John Dawson, chairman of EuroRAP.
"But most rural roads in Europe are not safe at the posted speed limit.
"Most deaths happen on busy one or two-star main single carriageway roads that need urgent investment in affordable safety line markings, safety fencing and junction layouts."
The report argues that road crashes cost the British economy £18bn a year, with emergency services, long-term care and lost work-hours all contributing to the cost.
The foundation says a study should be carried out into the benefits of upgrading major roads.
It points out that the Dutch government committed itself to raising its network to a three-star minimum by 2020 after a similar study.
A Highways Agency spokesperson said EuroRap had recognised England's roads were safe by awarding three or four stars for all its motorways and 98% of dual carriageways.
"Single-carriageway roads - which represent one fifth of the Highways Agency network - are by their very nature less likely to score as highly as motorways and dual carriageways," the spokesperson said.
"But we fund this work by EuroRAP to help us identify where to focus improvements and are committed to working with road safety organisations to continue to make all our roads safer."
Professor Stephen Glaister, director of the RAC Foundation, said that in many cases it was not going too fast that killed but what vehicles hit when they left the road in an accident.
He said: "Simple engineering solutions offer extraordinary rates of return for every pound spent.
"The cost of accidents to the economy is enormous yet by spending its dwindling resources wisely the DfT [Department for Transport] could have a big impact on road casualty rates and get great value for money."