More than 1,700 people had been injured.
Many more are feared trapped under rubble, officials say.
The 7.8 magnitude earthquake struck an area between the capital, Kathmandu, and the city of Pokhara, the US Geological Survey said.
Tremors were felt across the region, with further loss of life in India, Bangladesh, Tibet and on Mount Everest.
The government has declared a state of emergency in the affected areas.
Nepali Information Minister Minendra Rijal said there had been “massive damage” at the epicenter, from where little information is emerging.
“We need support from the various international agencies which are more knowledgeable and equipped to handle the kind of emergency we face now,” he said.
The US is sending a disaster response team to Nepal and has released an initial $1 million to address immediate needs, the USAid has said.
Rescuers are digging through the rubble of collapsed buildings in the capital trying to reach survivors, as thousands prepare to spend the night outside as darkness fell.
A number of historic buildings have been destroyed.
Among those wrecked was the landmark Dharahara tower, with many feared trapped in its ruins.
After the earthquake struck, frightened residents came out into the streets. Mobile phones and other communications have been disrupted.
There are also reports of damage to Kathmandu airport which could hamper relief operations.
With little known about the extent of the damage around the earthquake’s epicenter, there are fears the death toll could rise.
Aftershocks continued to ripple through the region hours later.
The tremor triggered an avalanche on Mount Everest, killing at least eight people, and another five in Tibet, officials and reports say.
At least 35 people have been killed in India, Indian officials say, with one death also reported in Bangladesh.
India’s PM Narendra Modi has met his ministers to review the situation. Pakistan’s PM Nawaz Sharif has pledged help for the Nepalese authorities.
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