It is the first direct US military action against Syria and its leader, Bashar al-Assad.
The attack against an air base in the west of the country comes in response to more than 80 civilian deaths from chemical weapons in a rebel-held town.
The Pentagon said it fired 59 Tomahawk cruise missiles at 4.40am (about 1.40pm NZT) from destroyers in the eastern Mediterranean.
The Syrian Observatory for Human Rights said the missile strikes killed at least four soldiers at the airbase.
