Attaullah Khogyani, the spokesman for Nangarhar's provincial governor, said the roof of the mosque had fallen in due to the blast and so far more than 20 were reported dead.
In western Herat province, six civilians were killed and five wounded when their vehicle was hit by roadside bomb, Jailani Farhad, spokesman for the provincial governor, said.
The blast took place as dozens of people gathered inside the mosque for weekly Friday prayers.
No group immediately claimed responsibility but the government accused Taliban insurgents, who are fighting to reimpose strict Islamic law after their 2001 ouster by US -led forces.
The blast came after the United Nations released a new report on Thursday saying that an "unprecedented" number of civilians were killed or wounded in Afghanistan from July to September.
He said 23 of the 50 wounded were transferred to Jalalabad, the provincial capital, and the rest of were being treated in the district clinic.
NOAA releases its winter outlook for 2019 El Niño is expected to remain neutral during the winter, meaning there will be neither El Niño or La Niña. He says predicting long-term winter weather is especially hard during the neutral phase of the El Nino.
USA and Afghan forces have conducted specific operations in recent months to target the Islamic State and drive them from eastern Afghanistan.
"Civilian casualties are totally unacceptable", said the UN's special representative in Afghanistan, Tadamichi Yamamoto, adding they demonstrate the importance of talks leading to a ceasefire and a permanent political settlement.
Sediq Sediqqi, spokesman for the presidential palace, condemned what he said was a suicide bomb attack. Insurgents were responsible for 62 percent.
The report said 2,563 civilians were killed and 5,676 were wounded in the first nine months of this year.
Khogyani said the victims include children who were at the mosque, and that the number of casualties could still rise.
The meeting was significant and the first that Khalilzad has held with the Taliban since last month, when President Donald Trump declared that the talks were 'dead, ' blaming an uptick in violence by the Taliban that included the killing of a United States soldier.