Calling the North a threat to global order, Mattis stood inside the Demilitarized Zone that separates the two Koreas and pledged solidarity with the South.
"We stand should to shoulder with you and the Korean people in confronting the threats posed by the Kim Jong Un regime," Mattis said as South Korean Defence Minister Song Young-moo looked on.
Mattis called the North "an oppressive regime that shackles its people, denying their freedom, their welfare and their human dignity in pursuit of nuclear weapons and their means of delivery in order to threaten others with catastrophe."
Mattis arrived in South Korea earlier Friday to meet with the nation's top defense officials and American military commanders on the front line in countering North Korea's nuclear weapons program.
More From This Section
Mattis is emphasising the Trump administration's push for a diplomatic solution to the problem. But he also has said the US is prepared to take military action if the North does not halt its development of missiles that could strike the entirety of the United States, potentially with a nuclear warhead.
Two other developments Thursday showed the US intention to continue building diplomatic and economic pressure on Pyongyang.
The Trump administration imposed sanctions on 10 North Korean officials and organizations over human rights abuses and censorship, including a diplomat in China accused of forcing North Korean asylum seekers home.
Trump entered office declaring his commitment to solving the North Korea problem, asserting that he would succeed where his predecessors had failed. His administration has sought to increase pressure on Pyongyang through UN Security Council sanctions and other diplomatic efforts, but the North hasn't budged from its goal of building a full-fledged nuclear arsenal, including missiles capable of striking the US mainland.