On 14 April 2018, beginning at 04:00 Syrian time (UTC+3), the United States, France, and the United Kingdom carried out a series of military strikes involving aircraft and ship-based missiles against multiple government sites in Syria during the Syrian Civil War. The strikes were a reprisal for the Douma chemical attack against civilians on 7 April, widely attributed to the Syrian government. The Syrian government called the airstrikes a violation of international law.

A Syrian government offensive to recapture the rebel-held Eastern Ghouta suburb began in February 2018. The offensive was condemned by Western media and human rights organizations for its reportedly brutal humanitarian consequences. By the beginning of April, Douma was one of the last rebel enclaves remaining in the region, with rebel group Jaysh al-Islam in control of the city. Russian and Syrian state media reported a deal between the rebel group and Russia to hand over Douma to government control. Other news agencies reported members of the rebel group claiming a deal had not been brokered and that Jaysh al-Islam would not surrender Douma. What followed was a suspected chemical attack carried out in the Syrian city of Douma on 7 April 2018, with at least 70 people reported killed. One pro-opposition source said that a thousand people suffered from the effects. The Jaysh al-Islam rebel group, which controlled Douma at the time, along with several medical, monitoring, and activist groups, including the pro-rebel White Helmets (Syria Civil Defence), all reported that two Syrian Air Force Mi-8 helicopters had dropped barrel bombs. The bombs were filled with chlorine gas and possibly sarin. The World Health Organization said it received reports from partner agencies that some 500 people arrived at health facilities showing "signs and symptoms consistent with exposure to toxic chemicals." On 6 July 2018, the OPCW produced an interim report stating that chlorine residues had been found at the two attack sites, although no organophosphorous nerve agents or their degradation products were detected.

As with previous incidents, France, the United Kingdom, the United States, and other nations accused the Syrian government of being responsible for the use of chemical weapons. Russia and Iran, the Syrian government's main allies, denied chemical weapons had been used, claiming it was a false flag operation. Russia has said video of the chemical attack was staged by members of the White Helmets. Syrian Arab News Agency (SANA) said that the Saudi Arabian-backed Jaysh al-Islam was making "chemical attack fabrications in an exposed and failed attempt to obstruct advances by the Syrian Arab Army".

In May 2017, French President Emmanuel Macron said the use of chemical weapons in Syria would be a red line requiring immediate reprisal. France and the United States cited positive urine and blood samples collected as proof of chlorine being used in Douma.

In the early hours of 9 April 2018, an airstrike was conducted against Tiyas Military Airbase in Syria. The United States denied launching the airstrike, and an Israeli spokeswoman declined to comment. On 10 April, an emergency United Nations Security Council meeting was held where competing solutions were presented on how to handle the response to the chemical attack; all were eventually vetoed by Russia. By 11 April, Western nations began to consider military action in Syria, seeking a "strong joint response." On the same day, the Syrian government said it invited the Organisation for the Prohibition of Chemical Weapons to investigate the sites of the attacks. "Syria is keen on cooperating with the OPCW to uncover the truth behind the allegations that some western sides have been advertising to justify their aggressive intentions," said SANA, quoting an official source in the Foreign Ministry. Russia denied chemical weapons were used, and on 13 April, blamed Britain for staging the event in order to provoke US airstrikes.

By 12 April, British Prime Minister Theresa May had ordered Royal Navy submarines in the Mediterranean to move within cruise missile range of Syria by the end of the week. British military sources later told The Times that days before the missile strikes a British Astute-class submarine armed with Tomahawk missiles and approaching within firing range of Syrian military targets was chased by "one, and possibly two" Russian Kilo-class submarines from the Russian Navy base at Tartus. The Russian submarines were supported by two frigates and an antisubmarine aircraft, while the British submarine was assisted by a US Navy P-8 Poseidon patrol aircraft. Ultimately, no British submarine took part in the strikes.

The United Nations Charter requires a mandate from the United Nations Security Council for sovereign states to use force for the purpose of maintaining international security, but not for acting in self-defence or the protection of populations threatened by extermination at the hands of their own government. Since the UN Charter came into effect in 1945, military action in retaliation or reprisal to the act of another state has been prohibited; but a reprisal may be justified if its aim is to force the other state into compliance with its international obligations. Russia's use of its veto meant there was no prospect of the Security Council authorizing the use of force. Therefore, military action relies on an international public order argument based on defending the credibility of the prohibition of the use of chemical weapons, enforcing Syria's obligations under the terms of its membership of the Chemical Weapons Convention, and protecting civilians from further chemical weapon attacks to alleviate humanitarian suffering.

The strikes came hours before inspectors from the OPCW Fact-Finding Mission were due to arrive in Syria to investigate the attack.