The MV Cape Ray container ship "will be anchored from today at the Rota naval base in a routine visit" for rest and supplies on Spain's south coast, the US embassy said in a statement.
"When Syria has fulfilled the order of the United Nations to hand over the chemical products, the Cape Ray will leave Rota for a port in Italy where they will be loaded," the statement said.
The "neutralization" of the weapons will be carried out on board in international waters under a UN-sanctioned agreement, it added.
The Cape Ray set off from Virginia on January 27 bound for the southern Italian port of Gioia Tauro.
The dangerous cargo will include mustard gas and ingredients for nerve agents such as sarin.
The 650-foot (nearly 200-metre) cargo ship has been fitted with two big hydrolysis systems designed to neutralise lethal chemical agents.
The ship has a crew of 35 civilians operating the vessel and a 63-member team in charge of the hydrolysis units as well as a security force on board.
The United States has promised the operation does not pose an environmental threat.
Under a UN resolution based on a deal hammered out by the United States and Russia, Syria is to turn over all its chemical weapons for destruction in Syria or abroad.
A third shipment of chemical material left Syria on Monday, but Damascus has missed several key deadlines to move material and UN officials have urged it to speed up the process.
The Syrian government says it remains committed to the deadline of June 30, 2014 to destroy its entire chemical arsenal but that the ongoing civil war there was causing delays.
The deal to destroy Syria's chemical arms came after an August 2013 chemical weapons attack on the outskirts of Damascus that reportedly killed hundreds of civilians.
Washington and the Syrian opposition blamed the attack on the regime of President Bashar al-Assad, which denied responsibility.