In the latest incident, the Pentagon said a US F-15 aircraft flying over Syrian territory fired on the drone after it displayed hostile intent and advanced on coalition forces.
Earlier this month, the US shot down another pro-regime drone in the same area after it dropped munitions near coalition forces.
On several occasions in recent weeks, warplanes of the US-led coalition have also struck pro-government forces to prevent them advancing from the Al Tanf garrison in south-eastern Syria at a spot where the country's borders join Iraq and Jordan.
The incident took place after a series of clashes between pro-regime troops and the US-backed anti-ISIS group, the Syrian Democratic Forces, near the SDF-held town of Ja'Din, just south of Tabqah, Syria.
Davis said the USA did not attempt to dissuade the drone from advancing through an established communications line with Russian Federation, which is allied to the Syrian government but does not have command of forces aligned with it, because "the incident emerged very quickly". According to Washington sources, the jet had bombed US -backed forces.
Tuesday's encounter is the latest development in what's become an increasingly hostile standoff between the USA military and the various forces supporting Syrian President Bashar al-Assad's fight to stay in power.
As well as announcing that US-led coalition warplanes would be tracked, Russia's ministry of defence suspended a hotline set up to avoid clashes between United States and Russian aircraft over Syria.
The row prompted the Australian government to announce that it would "temporarily" halt its airstrikes in Syria.
LaVar Ball in talks to appear on Monday Night Raw
We expect a Ball jersey hanging up there one day, all right? Owners of 16 National Basketball Association championships, the Lakers have missed the playoffs in each of the last four seasons.
The U.S. responded forcefully Monday to the Russian threat. That means intimidating the USA into inaction while they crush opposition forces.
Another day, another escalation in Syria.
"The coalition presence in Syria addresses the imminent threat ISIS in Syria poses globally", the USA military said in a statement, referring to the Islamic State group, which controls a swath of territory in eastern Syria.
CNN has learned new details of Sunday's rare air-to-air encounter between a Syrian Su-22 fighter and two US Navy F/A-18E Super Hornets in the skies over Syria, the first time a US warplane has downed a manned aircraft since 1999. The U.S. military has established a roughly 50-kilometer "deconfliction" ring around Tanf, warning the pro-Assad Iranian-backed forces through a Russian deconfliction channel that movement within the zone could be considered hostile.
The missiles were apparently in response to an IS-claimed attack on the Iranian parliament earlier this month which killed more than a dozen people.
Both the United States and Russian Federation contend their forces are in Syria to fight ISIS.
Meanwhile, the United States and Russian militaries swapped accusations about an unsafe intercept involving a USA spy plane and a Russian fighter jet over the Baltic Sea.
"The Syrian regime ... needs to understand that we will keep the right of self-defense of coalition forces aligned against ISIS", he said.