The GBU-43/B Massive Ordnance Air Blast bomb, or MOAB, was dropped Thursday night on a network of fortified underground tunnels that ISIS had been using to stage attacks on government forces.
The strike in Nangarhar province near the Pakistan border killed 36 ISIS fighters, Afghan officials said. The US military previously estimated ISIS had 600 to 800 active fighters in the area but was unclear whether it had hoped to strike more.
The blast destroyed three underground tunnels as well as weapons and ammunition, but no civilians were hurt, Afghan and US officials said.
However, ISIS denied that any of its fighters were killed or injured, according to a statement in Arabic distributed by the terror group's media wing, Amaq News Agency.
The US military was quizzed Friday on whether the 21,600-pound behemoth, known as the "mother of all bombs" for its extraordinary force, was necessary for that particular target.
The GPS-guided bomb is capable of destroying an area equivalent to nine city blocks.
"This was the right weapon against the right target," Gen. John Nicholson, commander for US forces in Afghanistan, told a press conference.
"It was the right time to use it tactically against the right target on the battlefield."
Nicholson gave a vague response to reporters' questions on who ordered or greenlighted the strike, saying only that he enjoyed a certain amount of "latitude" to make decisions in his chain of command.
The general confirmed the strike was carried out in coordination with Afghan officials and said rigorous surveillance had been conducted to prevent any civilian deaths.
"Let me be clear -- we will not relent in our mission to fight alongside our Afghan comrades to destroy ISIS-K in 2017," he said, referring to the terror group's regional branch.
Afghan President Ashraf Ghani said he approved of the strike and that it was designed to support Afghan and US forces conducting clearance operations in the region.
But former President Hamid Karzai accused the United States of using Afghanistan as "a testing ground for new and dangerous weapons.
Scrutiny over US strikes
The bomb was dropped as Washington faces increased scrutiny over its military actions in the Middle East, including three US-led airstrikes in the past month that reportedly have killed civilians or allies.
On Tuesday, the US-led coalition in Syria killed 18 of its own allies
from the Syrian Democratic Forces in what was described as a misdirected airstrike. The United States is also investigating two strikes in Iraq and Syria, which Iraqi officials and activists in Syria say killed dozens of civilians.
But President Donald Trump said Thursday that the Afghanistan bombing was "another successful job."
The bombing -- along with the first US military strikes against the Syrian regime
last week -- mark a dramatic change in attitude for Trump
, who advocated an isolationist, "America first" foreign policy during his election campaign.
In just the last week, Trump has overseen the use of some of the most powerful weaponry in the US arsenal
He once said the invasion of Afghanistan was a mistake
, though he later walked back that statement, saying he "always supported" US involvement in the country.
A deafening blast
Residents in Afghan villages kilometers away from the target area felt Thursday's powerful strike.
One resident living around 2 kilometers (1.5 miles) from the blast told CNN he heard an "extremely loud boom that smashed the windows of our house."
"We were all scared, and my children and my wife were crying. We thought it had happened right in front of our house," he said.
"I have witnessed a countless number of explosions and bombings in the last 30 years of war in Afghanistan, but this one was more powerful than any other bomb as far as I remember."
Another Afghan man, 46-year-old Abdul, who lives 3 kilometers from the site, described the thick cloud of dust that formed after the deafening blast.
"We were unable to see each other at home because of the excessive dust inside the room," he said.
"I was feeling that boom till the morning."
Hamdullah Mohib, Afghanistan's ambassador to the United States, said the colossal MOAB was dropped after fighting had intensified over the last week. US and Afghan forces had been unable to advance because ISIS -- which has expanded into Afghanistan in recent years
-- had mined the area with explosives.
Locals told CNN that more than 3,000 families had fled the district in the past year or so since the militant group established its presence.
One man, who did not want to give his name for fear of ISIS retaliation, said there were no civilians left in the area the group controlled.
The region butts up against the porous Pakistan border. The rocky landscape is dotted with caves and defensive tunnels, making it easy to hold and hard to attack, according to Nic Robertson, CNN's international diplomatic editor
, who has reported from the Afghan mountains.
Afghanistan War 'at its lowest point'
The war in Afghanistan has largely slipped from public consciousness, replaced by the conflict in Syria
and ongoing tensions over North Korea
, but there are still around 8,400 US troops in the country
engaged in counterterrorism operations.
Those troops are separate from a wider NATO-led effort to train, advise and assist the Afghan army and police force.
Testifying before the Senate Armed Services Committee in February
, Nicholson, the commander, warned of a stalemate in Afghanistan. He told US lawmakers the current troop level was insufficient and there was a "shortfall of a few thousand" advisers to train the Afghans.
According to CNN national security analyst Peter Bergen
, "the war in Afghanistan is at its lowest point for the Afghans and their American allies since the Taliban were overthrown in the months after 9/11."
The Taliban "control or contest" about a third of the population of the country, Bergen said, citing senior US military officials. That's around 10 million people -- more than the population ISIS controlled in Syria and Iraq at the height of its power during the summer of 2014, he said.
First MOAB strike
Thursday marked the first time a MOAB has been used in the battlefield, according to US officials. Developed during the Iraq War, the munition is an air blast-type warhead that explodes before hitting the ground to project a massive blast from all sides.
During the final stages of testing in 2003
, military officials told CNN the MOAB was mainly conceived as a weapon employed for "psychological operations."
Military officials said then they hoped such a huge blast would rattle Iraqi troops and pressure them into surrendering or not even fighting.
As originally conceived, the MOAB was to be used against large formations of troops and equipment or hardened above-ground bunkers. The target set has been expanded to include targets buried under softer surfaces, such as caves or tunnels.