"THAAD is for defense of our ally's people, of our troops who are committed to their defense", Mattis said when he arrived in South Korea.
Mattis began a lightning-fast visit to Asia this week - the first foreign trip by a member of President Trump's still-incomplete Cabinet - less than two weeks after being sworn in as the Pentagon boss.
The commitment was made after Mattis met South Korea's acting president and prime minister, Hwang Kyo-ahn, in Seoul.
Hwang also told Mattis that the two countries could "induce changes of the North's method of calculation by strengthening sanctions and pressures" in close cooperation with the global community.
His visit comes amid heightened tension in Northeast Asia and the United States after North Korean leader Kim Jong-un declared in a New Year's speech on January 1 that the regime was in its "final stage" of test-firing an intercontinental ballistic missile (ICBM), the first of its kind.
Mattis' trip was seen by many as a signal that the Trump administration's foreign policy would focus on Asia.
"Together we confront the North Korean situation", he said, according to a Pentagon statement.
"We have to regret the reality of the threat that your country and my country faces".
Washington's proposed deployment of the sophisticated defence missile system, Terminal High Altitude Area Defence (Thaad), in the Korean peninsula is likely to dominate the talks between the two countries.
Mattis said the new U.S. administration takes over "the U.S. -ROK relations with strong trust" and promised that the bilateral alliance would be "further strengthened during his term".
Mattis clarified that the deployment is in no way an affront on China, saying that the "only reason" this matter under discussion is "North Korea's activities".
While Mattis' visit comes at a time when the North has been relatively quiet on the nuclear front, experts believe that the calm may be short-lived.
Trump hasn't said much about North Korea since.
But on the campaign trail a year ago, Trump said he might be willing to meet the North Korean leader for discussions over a hamburger. Last week, a United States based think-tank said the North appeared to have restarted a nuclear reactor at Yongbyon capable of processing plutonium for a nuclear weapon.
"The main reason why the U.S. is strengthening its allies with South Korea is to contain China", he said.
"South Korea and the United States must try to extract a change in North Korea's strategic calculus by deterring the North's aggression", Mr Hwang said in a statement.
Mattis made clear ahead of his trip that he would not be announcing changes to US policy - like demanding that America's key Asian allies start paying more.
Mattis and his counterpart Han Min-koo will hold talks on Friday morning at the South Korean defense ministry's headquarters. Its president, Park Geun-hye, had her duties suspended last month after impeachment over corruption allegations. The president has also pulled out of a major trade deal with Asian allies.