"A combined operation with the armed forces of France and the United Kingdom is now underway," President Trump said in an address to the nation.
Explosions were reported near the Syrian capital Damascus.
"We are prepared to sustain this response until the Syrian regime stops its use of prohibited chemical agents," President Trump said.
UK Prime Minister Theresa May confirmed British involvement, saying there was "no practicable alternative to the use of force".
But she also said the strikes were not about "regime change".
UK strikes carried out by four Tornado jets hit a military site near the city of Homs, which is believed to have housed precursor materials for chemical weapons, the ministry of defence said.
French President Emmanuel Macron also confirmed his country's participation in the operation.
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The US president said the purpose was "to establish a strong deterrent against the production, spread and use of chemical weapons".
"These are not the actions of a man, they are the crimes of a monster instead," he said of Syrian President Bashar al-Assad.
Syria has denied carrying out the attack and its ally, Russia, had warned that Western military strikes would risk starting a war.
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A US official told Reuters news agency that Tomahawk cruise missiles were being used against multiple locations in Syria.
The agency also quoted a witness in Damascus as saying "at least six loud explosions" were heard in the capital.
Syrian state television also confirmed strikes on Damascus. The country's air defences have also been deployed, reports say.
British-based monitoring group the Syrian Observatory for Human Rights said strikes had hit the Syrian Scientific Research Facility in the capital, along with several military sites.
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