A US official said 59 precision guided missiles hit Shayrat Airfield in Syria, where Washington believes Tuesday's deadly attack was launched.
"On Tuesday, Syrian dictator Bashar al-Assad launched a horrible chemical weapons attack on innocent civilians using a deadly nerve agent," Trump said in a televised address from his Mar-a-Lago estate in Florida.
"Tonight I call on all civilized nations to join us in seeking to end this slaughter and bloodshed in Syria and also to end terrorism of all kinds and all types," he said.
"We hope that as long as America stands for justice, then peace and harmony will in the end prevail."
Trump said the strikes were in the United States "vital national security interest." Syrian state TV called them acts of "aggression."
US military action against Syrian President Bashar al-Assad's regime marks a startling about-face for Trump, and a crucial shift in American involvement in Syria's grueling six-year civil war.
Pentagon statement on Syria airstrikes pic.twitter.com/ITuTEUTQFs— David Mack (@davidmackau) April 7, 2017
US Secretary of State Rex Tillerson had earlier Thursday vowed an "appropriate response" to the attack in Khan Sheikhun in rebel-held Idlib province.
Twenty-seven children were among the dead, and Turkey believes victims were exposed to the nerve agent sarin.
"What happened in Syria is truly one of the egregious crimes," Trump said earlier Thursday. "I guess he's running things, so I guess something should happen."
Trump's comments came as Tillerson — who like the president was in Florida to welcome China's Xi Jinping — called for "a political process that would lead to Assad leaving" and said his future role in the country was "uncertain."
The US ambassador to the UN, Nikki Haley, has warned that Washington could take unilateral action if the world body fails to respond to the allegations of chemical weapons use.
Military action brings enormous risks, as strikes could be subject to skirting Russian air defenses. Moscow also has advisors on the ground in Syria.