Unveiling the new defence strategy, Mattis told a Washington audience great power competitionnot terrorismis now the primary focus of America's national security.
As a result he sought to increase the lethality of the American military.
In an apparent reference to Russia, he warned against "threaten[ing] America's experiment in democracy".
"If you challenge us, it will be your longest and worst day," he warned during his speech at the John Hopkins.
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"This strategy is fit for our timeproviding the American people the military required to protect our way of life, stand with our allies, and live up to our responsibility to pass intact to the next generation those freedoms we enjoy today," he said.
Rogue regimes like North Korea & Iran persist in taking outlaw actions that threaten regional and even global stability, he said, adding that oppressing their own people and shredding their dignity and human rights, they push their warped views outward.
"We face growing threats from revisionist powers as different as China and Russia, nations that seek to create a world consistent with their authoritarian modelspursuing veto authority over other nation's economic, diplomatic, and security decisions," he said.
As part of the defence strategy, he said the US is going to build a more lethal force, will strengthen traditional alliances while building new partnerships with other nations.
The 14-page unclassified version of the national defence strategy said that one of its objective is maintaining favourable regional balances of power in the Indo-Pacific, Europe, the Middle East, and the Western Hemisphere.
"A free and open Indo-Pacific region provides prosperity and security for all. We will strengthen our alliances and partnerships in the Indo-Pacific to a networked security architecture capable of deterring aggression, maintaining stability, and ensuring free access to common domains," the strategy said.
China, it said, is leveraging military modernisation, influence operations, and "predatory economics to coerce neighbouring countries" to reorder the Indo-Pacific region to their advantage.
As China continues its economic and military ascendance, asserting power through an all-of-nation long-term strategy, it will continue to pursue a military modernisation program that seeks Indo-Pacific regional hegemony in the near-term and displacement of the United States to achieve global preeminence in the future.
"Concurrently, Russia seeks veto authority over nations on its periphery in terms of their governmental, economic, and diplomatic decisions, to shatter the North Atlantic Treaty Organisation and change European and Middle East security and economic structures to its favour," it said.
The use of emerging technologies to discredit and subvert democratic processes in Georgia, Crimea, and eastern Ukraine is concern enough, but when coupled with its expanding and modernising nuclear arsenal the challenge is clear, the strategy said.