"We stand firmly, 100 per cent, shoulder-to-shoulder with you and (the) Japanese people," Mattis told Japanese Prime Minister Shinzo Abe after arriving on his first visit since the inauguration of US President Donald Trump.
"I wanted to make certain that Article Five of our mutual defence treaty is understood to be as real to us today as it was a year ago, five years ago and it will be a year and 10 years from now," he added in remarks at the start of their meeting.
Mattis arrived from South Korea and his visit marks the first overseas trip of any senior official from US President Donald Trump's administration, who suggested while campaigning that America's longstanding role in Northeast Asia could change.
On the campaign trail, Trump raised the possibility of Japan and South Korea arming themselves with nuclear weapons, and accused Seoul and Tokyo of not paying their fair share for US troops stationed in their countries.
Some 47,000 US troops are stationed in Japan and another 28,500 in South Korea.
"I do have a hope, and also I am convinced, together with you and President Trump we will be able to demonstrate the unwavering alliance between Japan and the United State both to the public inside Japan as well as outside Japan," Abe said.
He also praised Mattis, who is scheduled to meet Japan's defence minister on Saturday, as the right person for the job of US defence chief.
"I was very encouraged to see someone like you who has substantial experience both in the military, as well as security, defence and diplomacy taking this office," he said.
Before leaving South Korea, Mattis said that any nuclear attack by North Korea would trigger an "effective and overwhelming" response.
"Any attack on the United States or our allies will be defeated and any use of nuclear weapons would be met with a response that would be effective and overwhelming," Mattis told reporters ahead of a meeting with his South Korean counterpart Han Min-Koo.
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