The president made "absolutely clear" during a Monday speech at the National Defense University in Washington that the use of chemical weapons by the Assad government against rebel fighters "would be totally unacceptable " and trigger an immediate and overwhelming response by the United States.
The president's comments come amid reports that government troops have begun to move chemical weapons stockpiles out of storage, raising the prospect of those weapons being used in the Syrian civil war, which has lasted for more than a year.
Assad forces began shuffling around previously undisclosed stockpiles of sarin nerve agent, mustard gas and cyanide to various parts of Syria beginning in July.
"These are unacceptable risks for the United States and the entire international community, and they would threaten our vital national security interests," Sens. John McCain (R-Ariz.), Joe Lieberman (I-Conn.) and Lindsey Graham (R-S.C.) said at the time, regarding the possible use of chemical weapons in Syria.
If deployed, the weapons would not only pose a threat to Syrian civilians but to the United States and its allies, should terror groups like al Qaeda get a hold of the deadly ordnance, Rep. Mike Rogers (R-Mich.), head of the House Permanent Select Committee on Intelligence, warned in July.
"I am very concerned that as the situation in Syria deteriorates, these weapons could fall into the wrong hands," Rogers said.
Defense Secretary Leon Panetta confirmed in September that U.S. intelligence officials have confirmed the location of the major caches of chemical weapons inside Syria.
However, the DOD chief admitted that American military and intelligence leaders have not been able to track a number of the smaller, more mobile weapon stockpiles in Assad's arsenal.
Further, the Pentagon or CIA were not able to confirm whether Damascus still had control of those rogue weapons, according to Panetta.
"There has been intelligence that there have been some moves that have taken place. Where exactly that's taken place, we don't know," he said at the time.
U.S. and NATO forces were unprepared to secure Libya's stockpiles of shoulder-fired rockets after former Libyan dictator Moammar Gadhafi was killed last March by anti-government rebels in that country.
Last October, U.S. intelligence allegedly picked up "worrying indicators" that the missiles, similar to the famous Stinger anti-aircraft missile that the United States supplied to the Afghans to defeat the Soviets, had made their way to Islamic terror groups operating in the region.