A ship loaded with 331 kg (730 lb) of weapons-grade plutonium -enough to make 50 nuclear bombs- left Japan for the United States on Tuesday.
The stockpile, provided by the US, Britain and France decades ago for research purposes, is being shipped as part of an agreement to transfer the material to the US reached in March 2014, International Panel on Fissile Materials said.
Anti-nuclear campaign groups said it will take two months for the ship to arrive at a nuclear facility in South Carolina.
The shipment "exposes the failure of global plutonium reprocessing programmes and the threat from current Japanese nuclear policy," five anti-nuclear groups including Greenpeace said in a joint statement.
It is a tiny portion of Japan’s nearly 50 tonnes of plutonium. Japan traditionally has relied heavily on nuclear technology for its energy needs, though after a meltdown in Fukushima nuclear plant in 2011 led to all but two of the country's reactors being shut down.
The US will hold the Nuclear Security Summit later this month, and the shipment is meant to underscore both countries' commitment to nuclear non-proliferation.
But anti-nuclear campaigners including Greenpeace last week condemned the shipment as a "dangerous distraction" from a far larger cache of the plutonium in the country.
Japan has the know-how of how to make a nuclear weapon, which brought condemnation from neighbouring countries also.
China called on Japan to take further steps to reduce its stock.
"In addition, it should return large quantities of other materials, including weapons-grade plutonium and enriched uranium," foreign ministry spokeswoman Hua Chunying told reporters.
"This is indeed a concern of the international community."