On President Donald Trump's orders, US warships in the Mediterranean Sea launched between 50-60 Tomahawk cruise missiles at the Shayrat air base, in Homs governorate, where the warplanes that carried out the chemical attacks are based, US officials said.
The move signals a dramatic shift in Trump's position on whether the US should take military action against Assad's regime. Trump, during his campaign for president, had opposed any such move.
Speaking from his Mar-a-Lago resort in Florida, Trump said he ordered targeted missile strikes at the Syrian airfield.
A military official quoted on Syrian TV said the US action caused material damage.
Describing the chemical attack on innocent civilians as "horrible", Trump said President Assad took the lives of helpless men, women and children.
"It was a slow and brutal death for so many. Even beautiful babies were cruelly murdered in this very barbaric attack. No child of God should ever suffer such horror," he said.
The military action comes after Tuesday's deadly chemical attack that officials said used chlorine mixed with a nerve agent, killing 86 people, including 27 children, in the rebel-held town of Khan Sheikhun in northwestern Syria.
This is the first direct military action the US has taken against the regime of Assad in Syria's six-year civil war and represents a substantial escalation of the US military campaign in the region.
"There can be no dispute that Syria used the banned chemical weapon violated its obligations under the chemicals weapons convention and ignored the urging of the UN Security Council," he said.
"We asked for God's wisdom as we face the challenge of our very troubled world. We pray for the lives of the wounded and for the souls of those who passed. And we hope as long as America stands for justice and peace and harmony will in the end prevail. Good night and God Bless America and the entire world," Trump said in his brief remarks before his first meeting with his Chinese counterpart Xi Jinping.
"Clearly Russia has failed in its responsibility. Either Russia has been complicit or either Russia has been simply incompetent in its ability to deliver on its end of that agreement," Tillerson told reporters.
He said that the US has a very "high level of confidence" that the chemical attacks were carried out under the direction of Assad's regime.
"We have very high confidence that the attacks involved the use of sarin nerve gas," he said.
Pentagon Press Secretary Captain Jeff Davis said Russian forces were notified in advance of the strike using the established deconfliction line.
"US military planners took precautions to minimise risk to Russian or Syrian personnel located at the airfield," he said.
The Pentagon said the missile strike that targeted Shayrat Airfield was a proportional response to Assad's heinous act.
"The strike was a proportional response to Assad's heinous act. Shayrat Airfield was used to store chemical weapons and Syrian air forces. The US intelligence community assesses that aircraft from Shayrat conducted the chemical weapons attack on April 4," Davis said.
"Russian forces were notified in advance of the strike using the established deconfliction line. US military planners took precautions to minimise risk to Russian or Syrian personnel located at the airfield," Davis said.
The deaths of civilians in Syria sparked international outrage with many pointing the finger at the government of President Assad.
The UK, Israel and Australia were among the countries backing Trump's move as an "appropriate" and "just" response.
The Syrian army on Tuesday denied that it had used chemical weapons against Khan Sheikhun.
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