The Iranian-made drone had displayed "hostile intent" while approaching an allied outpost, the US-led coalition reported. The coalition said it would not "tolerate any hostile intent and action of pro-regime forces."
"When the armed UAV (drone) continued to advance on the coalition position without diverting its course, it was shot down," said a statement from Operation Inherent Resolve.
The incident marks the third time US-led forces have shot down an aircraft affiliated to the government of Syrian President Bashar al-Assad in June.
On Sunday, the US military downed a Syrian warplane near Raqqa after the aircraft dropped munitions near the US-backed Syrian Democratic Forces battling to recapture the city from IS.
Targeting 'imminent threat'
The move raised tensions between the Syrian government and its allies on one side and the US-led coalition on the other. Russia suspended a military backchannel and on Monday threatened to target coalition aircraft that traveled west of the Euphrates River. But the US remained steadfast in its decision, saying the coalition would not "tolerate any hostile intent and action of pro-regime forces."
"The coalition presence in Syria addresses the imminent threat ISIS in Syria poses globally," the statement said. "The coalition does not seek to fight the Syrian regime, Russian or pro-regime forces partnered with them, but will not hesitate to defend the coalition or partner forces from any threat."
More than 300,000 people have been killed and half the population in Syria displaced since 2011, when regime forces launched a brutal crackdown on peaceful protesters calling for the release of political prisoners and for Assad to step down.
Since then, it has fractured into a multi-faceted conflict involving global superpowers, regional actors, terrorist organizations and rebel groups.
Who's fighting in the Syria conflict?
Syria's civil war erupted out of the Arab Spring protests that swept much of the Middle East and North Africa in 2011. The conflict has since drawn in multiple warring factions from around the world.
Image: Atta Kenare/AFP/Getty Images
War with no end
Syria has been engulfed in a devastating civil war since 2011 after Syrian President Bashar Assad lost control over large parts of the country to multiple revolutionary groups. The conflict has since drawn in foreign powers and brought misery and death to Syrians.
Image: picture alliance/abaca/A. Al-Bushy
The dictator
Syria's army, officially known as the Syrian Arab Army (SAA), is loyal to Syrian President Bashar al-Assad and is fighting to restore the president's rule over the entire country. The SAA has been fighting alongside a number of pro-Assad militias such as the National Defense Force and has cooperated with military advisors from Russia and Iran, which back Assad.
Turkey, which is also part of the US-led coalition against IS, has actively supported rebels opposed to Assad. It has a tense relationship with its American allies over US cooperation with Kurdish fighters, who Ankara says are linked to the Kurdistan Workers' Party (PKK) fighting in Turkey. Turkey has launched multiple military offensives targeting Kurdish militias.
Image: picture-alliance/AP Photo/L. Pitarakis
The eastern guardian
The Kremlin has proven to be a powerful friend to Assad. Russian air power and ground troops officially joined the fight in September 2015 after years of supplying the Syrian army. Moscow has come under fire from the international community for the high number of civilian casualties during its airstrikes. However, Russia's intervention turned the tide in war in favor of Assad.
Image: picture-alliance/dpa/Tass/M. Metzel
The western allies
A US-led coalition of more than 50 countries, including Germany, began targeting IS and other terrorist targets with airstrikes in late 2014. The anti-IS coalition has dealt major setbacks to the militant group. The US has more than a thousand special forces in the country backing the Syrian Democratic Forces.
Image: picture alliance/AP Photo/A.Brandon
The rebels
The Free Syrian Army grew out of protests against the Assad regime that eventually turned violent. Along with other non-jihadist rebel groups, it seeks the ouster of President Assad and democratic elections. After suffering a number of defeats, many of its members defected to hardline militant groups. It garnered some support from the US and Turkey, but its strength has been greatly diminished.
Image: Reuters
The resistance
Fighting between Syrian Kurds and Islamists has become its own conflict. The US-led coalition against the "Islamic State" has backed the Syrian Democratic Forces, an alliance of Kurdish and Arab militias. The Kurdish YPG militia is the main component of the SDF. The Kurds have had a tacit understanding with Assad.
Image: Getty Images/A. Sik
The new jihadists
"Islamic State" (IS) took advantage of regional chaos to capture vast swathes of territory in Iraq and Syria in 2014. Seeking to establish its own "caliphate," IS has become infamous for its fundamentalist brand of Islam and its mass atrocities. IS is on the brink of defeat after the US and Russia led separate military campaigns against the militant group.
Image: picture alliance/AP Photo
The old jihadists
IS is not the only terrorist group that has ravaged Syria. A number of jihadist militant groups are fighting in the conflict, warring against various rebel factions and the Assad regime. One of the main jihadist factions is Hay'at Tahrir al-Sham, which controls most of Idlib province and has ties with al-Qaeda.
Image: picture-alliance/AP Photo/Nusra Front on Twitter
The Persian shadow
Iran has supported Syria, its only Arab ally, for decades. Eager to maintain its ally, Tehran has provided Damascus with strategic assistance, military training and ground troops when the conflict emerged in 2011. The Iran-backed Lebanese Shiite militant group Hezbollah also supports the Assad regime, fighting alongside Iranian forces and paramilitary groups in the country.