It said some US officials feared the weapons could be used against rebels or civilians, while others believed the material was being deliberately hidden from armed opposition groups or Western powers.
"We have repeatedly made it clear that the Syrian government has a responsibility to safeguard its stockpiles of chemical weapons," spokeswoman for the US state department Victoria Nuland told reporters.
"The international community will hold accountable any Syrian officials who fail to meet that obligation," she added in a statement during a trip by secretary of state Hillary Clinton to Cambodia.
The Wall Street Journal said the Obama administration was "particularly worried about Syria's stocks of sarin gas, the deadly and versatile nerve agent".
Syria is also believed to have reserves of mustard gas and cyanide.
More than 17,000 people have been killed in violence since an uprising against Syrian President Bashar al-Assad's regime broke out in March last year, according to the Britain-based Syrian Observatory for Human Rights.