A specially-equipped US naval ship departed for Italy on Monday on a ground-breaking mission to destroy Syria's most dangerous chemical agents, Pentagon officials said.

After setting off from the port of Norfolk on the Virginia coast at 7:30 pm EST (0030 GMT Tuesday), the MV Cape Ray is due to arrive in the southern port of Gioia Tauro in about "two to three weeks," spokesman Colonel Steven Warren told reporters.

The 650-foot (197.5 meter) cargo ship has been outfitted with two large portable hydrolysis systems designed to neutralize lethal chemical agents in Syria's arsenal.

Defense Secretary Chuck Hagel sent a letter to Captain Rick Jordan and the 135-member crew telling them they were embarking on a "historic mission."

"You are about to accomplish something no one has tried," Hagel wrote in the letter released by the Defense Department.

"You will be destroying at sea one of the world's largest stockpiles of chemical weapons and helping make a safer world," he wrote.

The Cape Ray was initially supposed to head out earlier on Monday but engine problems delayed the scheduled departure, officials said.

The ship has a crew of 35 civilians operating the vessel and will have a 63-member team in charge of the hydrolysis units as well as a security force on board.

The hydrolysis machines will mix heated water and other chemicals to break down the lethal agents, resulting in a sludge equivalent to industrial toxic waste.

Last year, the UN Security Council last year backed a US-Russian deal to remove and destroy Syria's chemical arsenal.

The agreement was brokered as a way to avert US missile strikes that Washington threatened after a chemical attack near Damascus, which Washington and other Western governments blamed on the regime.

Under the accord, Syria's entire chemical arsenal is to be eliminated by June 30.

The arrangement will see some of the most dangerous agents neutralized on the US ship at sea, as no country was ready to host an operation to destroy the chemicals.

The chemicals will be loaded on to the Cape Ray at the Italian port and then taken to an undisclosed location for destruction. The Pentagon stressed the ship's work was not an environmental cause for alarm.

"No hydrolysis byproducts will be released into the sea or air. M/V Cape Ray will comply with all applicable international laws, regulations, and treaties," a spokesman said.

The materials are the deadliest in Syria's 1,290-tonne declared arsenal and include mustard gas and the ingredients for the nerve agents sarin and VX.

The destruction of the chemicals could take between 45 to 90 days, according to the Pentagon.