The most senior US general believes around 200,000 Russian and Ukrainian soldiers have been killed or injured in the war in Ukraine since hostilities began in February.
General Mark Milley, chairman of the US Joint Chiefs of Staff, also suggested that around 40,000 civilians have died after being caught up in the conflict.
The estimates are the highest offered yet by a Western official.
He also said that signs Kyiv was willing to re-enter talks with Moscow offered “a window” for negotiations.
In recent days, Ukraine has signalled a willingness to hold some discussions with Moscow, after President Volodymyr Zelensky dropped a demand that his opposite number, Vladimir Putin, must be removed from power before negotiations could resume.
But speaking in New York, Milley added that for any talks to be successful, both Russia and Ukraine would have to reach a “mutual recognition” that a wartime victory “is maybe not achievable through military means, and therefore you need to turn to other means”.
The top general – who serves as President Joe Biden’s most senior military adviser – said the scale of the casualties could convince both Moscow and Kyiv of the need to negotiate over the coming winter months, when fighting may slow due to freezing conditions.
“You’re looking at well over 100,000 Russian soldiers killed and wounded,” Milley said. “Same thing probably on the Ukrainian side.”
Both Ukraine and Russia jealously guard their casualty numbers.
Moscow’s last update in September said that just 5,937 troops had been killed since the start of the conflict, with Defence Minister Sergei Shoigu dismissing reports of a significantly higher death toll.
Milley’s estimate is starkly higher. By comparison, 15,000 Soviet soldiers were estimated to have died in the 1979-89 Afghanistan conflict.
Ukraine has largely refrained from giving casualty figures. But in August, the armed forces’ commander-in-chief, Valeriy Zaluzhniy, was quoted in Ukrainian media saying 9,000 Ukrainian soldiers had died so far.
The UN has said it does not consider figures released by those involved in the conflict to be reliable.
“There has been a tremendous amount of suffering, human suffering,” said Milley. He also also noted that between 15 and 30 million refugees have been created since Russia launched its invasion on 24 February.
The UN has recorded 7.8 million people as refugees from Ukraine across Europe, including Russia. However, the figure does not include those who have been forced to flee their homes but remain in Ukraine.
On Wednesday, Moscow announced its troops would start to withdraw from the key southern city of Kherson – the only major city to fall to Russian forces.
Gen Milley said that while “initial indicators” suggested that a retreat had begun, he observed that Russia had amassed around 20-30,000 troops in the city, and the withdrawal could take several weeks.
“They made the public announcement they’re doing it. I believe they’re doing it in order to preserve their force to re-establish defensive lines south of the [Dnieper] river, but that remains to be seen,” he said.
The news of Russia’s withdrawal from Kherson comes after Russian President Vladimir Putin called up some 300,000 reservists to fight in Ukraine in September.
Military experts in the West and Ukraine say the need for mobilisation showed that Russian troops were failing badly on the battlefield in Ukraine.