The destruction of Syria's chemical weapons began on 14 September 2013 after Syria entered into several international agreements which called for the elimination of Syria's chemical weapon stockpiles and set a destruction deadline of 30 June 2014. Also on 14 September 2013, Syria acceded to the Chemical Weapons Convention (CWC) and agreed to its provisional application pending its entry into force on 14 October. Having acceded to the CWC, the Organisation for the Prohibition of Chemical Weapons (OPCW) Executive Council on 27 September approved a detailed implementation plan that required Syria to assume responsibility for and follow a timeline for the destruction of Syrian chemical weapons (such as sarin) and Syrian chemical weapon production facilities. Following the signing of the Framework Agreement on 14 September 2013 and after the OPCW implementation plan, on 27 September the United Nations Security Council unanimously adopted Resolution 2118 which bound Syria to the timetable set out in the OPCW implementation plan. The joint OPCW-UN mission was established to oversee the implementation of the destruction program.

The OPCW began preliminary inspections of Syria's chemical weapons arsenal on 1 October 2013, and actual destruction began on 6 October. Under OPCW supervision, Syrian military personnel began "destroying munitions such as missile warheads and aerial bombs and disabling mobile and static mixing and filling units". The destruction of Syria's declared chemical weapons production, mixing, and filling equipment was successfully completed by 31 October deadline, but the destruction of chemical weapon stockpiles fell well behind schedule, which had been scheduled for completion by 6 February 2014. Only on 23 June 2014, were the remaining declared chemicals shipped out of Syria for destruction. The destruction of the most dangerous chemicals was performed at sea aboard the Cape Ray, a vessel of the United States Maritime Administration's Ready Reserve Force, crewed with U.S. Navy and civilian merchant mariners. The actual destruction operations, performed by a team of U.S. Army civilians and contractors, destroyed 600 metric tons of chemical agents in 42 days. By 18 August 2014, all of the remaining declared and surrendered chemicals had been destroyed offshore. On 4 January 2016, the OPCW stated that destruction was completed, though since then the use of chemical weapons on numerous occasions allegedly by the Syrian military has been verified.

The agreement by Syria to destroy its chemical weapons arose at a time when the United States and France headed a coalition of countries on the verge of carrying out air strikes on Syria in response to the 21 August 2013 Ghouta chemical-weapon attacks. To avoid a military intervention, on 14 September 2013, the United States, Russia and Syria agreed to the "Framework for Elimination of Syrian Chemical Weapons". Chlorine, a common industrial chemical, is outside the scope of the disarmament agreement; however, its use as a poison gas would violate the Chemical Weapons Convention, which Syria joined in 2013. Various parties, including Western governments, have accused Assad of conducting illegal chlorine attacks since 2014.Western officials, such as British Ambassador Mark Lyall Grant, had expressed concerns about the completeness of Syria's disclosures, and said the OPCW mission should remain in place following removal of chemical weapons until verification tasks can be completed. A late disclosure in 2014 regarding Syria's ricin program raised doubts about completeness of the government's declaration of its chemical weapons stockpile, and in early May 2015, OPCW announced that inspectors had found traces of sarin and VX nerve agent at a military research site in Syria that had not been declared previously by the Assad regime. Syria appeared to bomb Khan Shaykhun with sarin in April 2017. A chemical attack on Douma on 7 April 2018 that killed at least 49 civilians and injured scores more has been blamed on the Assad government, though the Syrian government disputes these charges.

Syria's chemical weapons program began in the 1970s with weapons and training from Egypt and the Soviet Union, with production of chemical weapons in Syria beginning in the mid-1980s. For some time, Syria was believed to have the world's third-largest stockpile of chemical weapons, after the United States and Russia. Prior to September 2013 Syria had not publicly admitted to possessing chemical weapons, although Western intelligence services believed it to hold one of the world's largest stockpiles. In September 2013, French intelligence put the Syrian stockpile at 1,000 tonnes, including Yperite, VX and "several hundred tonnes of sarin". At the time, Syria was one of a handful of states which had not ratified the Chemical Weapons Convention. In September 2013, Syria joined the CWC (formally acceding on 14 October), and agreed to the destruction of its weapons, to be supervised by the Organisation for the Prohibition of Chemical Weapons (OPCW), as required by the convention. A joint OPCW-United Nations mission was established to oversee the destruction process. Syria joined OPCW after international condemnation of the August 2013 Ghouta chemical attack, for which Western states held the Syrian government responsible (whilst Syria and Russia held the Syrian rebels of the Syrian civil war responsible) and agreed to the prompt destruction of its chemical weapons, resulting in U.S. Secretary of State John Kerry declaring on 20 July 2014: "we struck a deal where we got 100 percent of the chemical weapons out." The destruction of Syria's chemical weapons that the Assad government had declared was completed by August 2014, yet further disclosures, incomplete documentation, and allegations of withholding part of Syria's chemical weapons stockpile since mean that serious concerns regarding chemical weapons and related sites in Syria remain. On 5 April 2017, the government of Syria allegedly unleashed a chemical attack that killed 70 civilians. A suspected chemical attack on Douma on 9 April 2018 that killed at least 49 civilians has been blamed on the Syrian Government.