By Agence France-Presse
The GBU-43/B Massive Ordnance Air Blast bomb hit a "tunnel complex" in Achin district in Nangarhar province, US Forces Afghanistan said in a statement.
The strike occurred at 7:32 pm (1502 GMT).
"The GBU-43/B is the largest non-nuclear bomb ever deployed in combat," Air Force spokesman Colonel Pat Ryder said.
Pentagon spokesman Adam Stump said the bomb was delivered via an MC-130 transport plane.
"As (ISIS-Khorasan's) losses have mounted, they are using IEDs, bunkers and tunnels to thicken their defense," said General John Nicholson, who heads US Forces Afghanistan.
"This is the right munition to reduce these obstacles and maintain the momentum of our offensive against ISIS-K."
White House spokesman Sean Spicer said: "We must deny them operational space, which we did."
The MOAB is better known by its nickname, the Mother of All Bombs, and was rapidly developed in 2002-2003 around the time of the US-led invasion of Iraq.
According to the Air Force, the last time the MOAB was tested in 2003, a huge mushroom cloud could be seen from 20 miles (32 kilometers) away.