A Pentagon official said about 50 Tomahawk cruise missiles were fired from Navy destroyers in the eastern Mediterranean at a Syrian air base.
President Donald Trump said he ordered the strike against the base from where Tuesday's attack was launched.
He called on "all civilised nations" to help end the conflict in Syria.
Dozens of civilians died in the suspected nerve gas attack.
The missiles hit the Shayrat airfield, from where Washington believes Tuesday's deadly attack was launched, one US official was quoted as saying.
Earlier on Thursday, US Secretary of State Rex Tillerson said Syrian leader Bashar al-Assad should have no role in a future Syria.
His comments signalled a sudden shift in policy by the new US administration.
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