The US government added Ba'athist Syria, which seized power in 1963, to its first list of "State Sponsors of Terrorism" in 1979, over its funding of Palestinian and other insurgent factions in the region.

As a result of a failed 1957 CIA coup attempt to topple Syrian President Shukri al-Quwatli, Syria asked US Ambassador James S. Moose to leave Damascus.

"[citation needed] Also in 1986, the U.S. withdrew its ambassador and imposed additional administrative sanctions on Syria in response to evidence of direct Syrian involvement in an attempt to blow up an Israeli airplane.

A U.S. ambassador returned to Damascus in 1987, partially in response to positive Syrian actions against terrorism such as expelling the Abu Nidal Organization from Syria and helping free an American hostage earlier that year.

In 1991, Syrian President Hafez al-Assad made a historic decision to accept then-President Bush's invitation to attend a Middle East peace conference and to engage in subsequent bilateral negotiations with Israel.

Syria improved its relations with the United States by securing the release of Western hostages held in Lebanon and lifting the travel restrictions on Syrian Jews.

In one such case, Syrian intelligence alerted the U.S. of an al-Qaeda plan similar to the USS Cole bombing, which was to fly a hang glider loaded with explosives into the U.S. Navy's Fifth Fleet headquarters in Bahrain.

In May 2003, the U.S. Secretary of State, Colin Powell, visited Damascus to demand Syrian closure of the offices of Hamas, Islamic Jihad and the Popular Front for the Liberation of Palestine.

[19][20] Issues of U.S. concern include its ongoing interference in Lebanese affairs, its protection of the leadership of Palestinian rejectionist groups in Damascus, its human rights record, and its pursuit of weapons of mass destruction.

These sanctions are imposed on certain Syrian citizens or entities due to their participation in terrorism, acts of public corruption, or their destabilizing activities in Iraq and Lebanon.

[citation needed] In 2008, the CIA and the U.S. Joint Special Operations Command (JSOC) carried out a paramilitary raid targeting al-Qaeda in Iraq in the town of Sukkariyeh in Abu Kamal.

[26][27] Diplomatic cables between the US embassy in Damascus and the State Department that were released by WikiLeaks in 2011 revealed that, starting during the presidency of George W. Bush, the US gave financial support to political opposition groups and related projects, at least through September 2010.

According to the Council on Foreign Relations in 2010, Syria actively barred any Syrian-based terrorist attacks and targeting of Westerners, instead, providing “passive support” to groups it deems as legitimate resistance movements.

[31] Shortly after Ford's appointment, Under Secretary of State for Political Affairs William J. Burns arrived in Damascus and hosted talks with President Bashar al-Assad in an attempt to revive relations.

In meetings revolved around discussing "specific steps to promote regional stability, revive Syria–Israel peace talks, and strengthen U.S.–Syrian bilateral relations.

[34] The U.S. pushed strongly for the United Nations Security Council to pass a resolution condemning the Syrian government's measures to suppress the rebellion and adopting economic sanctions against Syria in late September and early October 2011, and when Russia and the People's Republic of China wielded their veto power to block the proposal, Ambassador Susan Rice expressed "outrage".

[35] Relations were further strained by Syrian security forces' failure to protect Robert Stephen Ford, the U.S. ambassador to Syria, from being attacked by pro-Assad crowds on at least two occasions, as well as to prevent vandalism of the U.S. embassy and diplomatic property.

"[37] After the revelation of the Houla massacre in May 2012, the U.S. State Department announced that Syrian chargé d'affaires in Washington had been given 72 hours to leave the country.

This letter argued against a U.S. bombing campaign against Syria, appealing to the two governments' common fight against Islamic extremism and blaming recent chemical weapons attacks on insurgents.

[57] On February 10, 2017, Syrian President Bashar al-Assad, while welcoming a notion that U.S. troops might fight alongside Syria, rejected the proposal for safe zones as "not a realistic idea at all".

[59] In December 2017, Max Abrams and John Glaser asserted in the Los Angeles Times that "[ISIL] imploded right after external support for the 'moderate' rebels dried up".

[66] On June 17, 2020, reports claimed that the US imposed tough new economic sanctions under the Caesar Act, targeting anyone doing business with the Syrian President Bashar al-Assad from anywhere in the world.

The sanctions were imposed to compel the Syrian government to halt its human rights abuses on civilians and accept a peaceful political transition.

[71] Following a series of rebel offensives that resulted in the fall of the Assad regime on 8 December 2024, and the establishment of a transitional government the next day, the two countries began to work together on a number of important issues that included combating Islamic State remnants in the Syrian Desert and locating American citizens recently freed from Assadist prisons.

[77] Relations have been strained by the lack of a harsh American response to the Israeli bombing campaign and incursions into Syria immediately after the establishment of the Transitional Government.

Al-Sharaa, who assumed leadership following the ousting of President Bashar al-Assad in December 2024, emphasized his administration's desire to improve relations between Syria and the United States through dialogue and understanding.

He highlighted the immense suffering Syria has endured over the past decade due to conflict and expressed optimism that under Trump's leadership, stability could be restored to the region.