The missile attack came amid recent confrontations in Syria between US -backed forces and Iranian-backed pro-government factions.
CBS News correspondent David Martin reports the drone came too close to one of the outposts of USA -backed fighters outside of their main base in Tanf.
Russian Federation made clear it was changing its military posture in response to the US downing of a Syrian military jet on Sunday, something Damascus said was the first such incident since the start of the country's conflict in 2011.
A defense official says the drone was considered a threat.
Russian Federation has denied USA claims that a communication channel was used to issue a warning to the jet before it was shot down.
"There has been neither a Security Council decision, nor a request from the official authorities of the Syrian Arab Republic as a sovereign state", Russia's Interfax news reported.
The US-led coalition said in a statement that an F-15E Strike Eagle jet destroyed the Shaheed-129 drone around 12:30 am local time northeast of the Al-Tanaf garrison, which is close to the Jordanian border.
Moscow also advised today that it was halting an incident-prevention hotline with Washington after USA forces downed a Syrian jet.
Syrian opposition activists say a truce that went into effect three days ago in the southern city of Daraa has collapsed amid a government offensive near the Jordanian border. The 48-hour truce that had started there at noon Saturday was supposed to be extended.
The top American general says the U.S. is working to restore a communications line with Russian Federation meant to avoid mid-air collisions over Syria, after Moscow cut it off following the USA downing of a Syrian military jet on Sunday.
Earlier this month, the US Air Force deployed long-range B-52 bombers and 800 airmen to the United Kingdom in support of joint exercises with North Atlantic Treaty Organisation allies and partners across Europe.
Previously Turkey shot down a Russian military plane, claiming it had crossed the official border into Turkish territory.
Daraa is where Syria's crisis first broke out in March 2011 as an uprising against President Bashar Assad's government. The conflict quickly descended into a civil war, which has since left at least 400,000 people dead. And the shot down place was near to the Syrian town of Tabqa.
According to Fox News, the Baltic region has had 35 USA and Russian interaction just this month and was the site of a US military training exercise, including the use of bombers and warships, leading to "heightened tensions with Russia".
"As a precautionary measure, Australian defense force strike operations into Syria have temporarily ceased", the Department of Defence said Tuesday. Israel also is concerned about Iran's missiles and has deployed a multilayered missile-defense system.