Gen John Nicholson, commander of US forces in Afghanistan and the man who signed off the use of the bomb, said the weapon had "achieved it's intended purpose" of eliminating several of the jihadis' underground bases in Nangarhar, close to the border with Pakistan.
An MC-130 aircraft dropped a GBU-43 – the largest non-nuclear bomb ever used in US combat history – on a cave complex believed to be populated by ISIS soldiers at about 7pm local time.
The Afghan defence minstry said up to 36 Islamic State militants were killed in the blast.
Gen Nicholson told a press briefing it was the "right time" to use the MOAB as part of the US Military's mission to wipe out ISIS in Afghanistan this year.
The use of IED belts and cave complexes presented siginificant obstacles to that objective, he said, which the bomb had now removed.
Gen Nicholson said: "This weapon was used on ISIS caves and their sanctuary inside Afghanistan.
"The purpose of this operation is to eliminate their sanctuary in Nangarhar.
"This weapon was very effective in that use. The weapon achieved it's intended purpose.
"This entire offensive, not just the use of a single weapon demonstrates the commitment of the Afghan army the Afghan special forces and their US partners to defeat Daesh in Afghanistan this year."
The US has dropped the 'mother of all bombs' on an ISIS cave complex in Afghanistan
The GBU-43/B Massive Ordnance Air Blast bomb
Gen Nicholson said the attack was "not related to any outside events other than our focus on destroying Daesh in 2017".
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"It was the right time to use it tactically, against the right target on the battlefield," he said.
The US Military had recorded as many as 20 different terrorist organisations in Afghanistan and Pakistan using the tunnels to communicate with each other,Gen Nicholson said, adding: "This is of great concern to us."
The GBU-43/B Massive Ordnance Air Blast bomb is a large non-nuclear explosive in the hands of the American military.
The MOAB weighs in at around 10,300 kg (22,600 lb) and is just over 9 m long in length. It has been lovingly dubbed the Mother Of All Bombs by the US military.
The explosive’s main purpose is to clear out swathes of land and targets hidden in canyons or caves.