A Syrian opposition monitor said the attack killed four soldiers, including a general. The head of the Britain-based Syrian Observatory for Human Rights said more than a dozen hangars, a fuel depot and an air defense base were damaged.
President Donald Trump said the attack on a Syrian air base was in the nation's "vital national security interest."
"Assad choked out the lives of helpless men, women and children," Trump said.
Tomahawk missiles were fired from two warships in the Mediterranean Sea, targeting a government-controlled air base in Syria, officials say.
U.S. officials said Syrian government aircraft killed dozens of civilians by using chlorine mixed with a nerve agent, possibly sarin, earlier this week.
Syrian state TV reported a U.S. missile attack on a number of military targets and called the attack an "aggression."
The Associated Press contributed to this report