Mr Mattis' sabre-rattling comes a day after Mr Trump issued a similar threat to Pyongyang.
By launching a volley of four, the North would be attempting to make it harder for the U.S.to intercept all of the incoming missiles.
While Trump was threatening annihilation and boasting from the New Jersey golf resort where he's vacationing that he has made the US nuclear arsenal "far stronger and more powerful than ever before", Secretary of State Rex Tillerson sought to calm the sense of crisis.
"The United States and our allies have the demonstrated capabilities and unquestionable commitment to defend ourselves from attack", he added. DPRK is short for the North's official name, the Democratic People's Republic of Korea.
Nelson says he's anxious North Korea's ability to put a nuclear device on a long-range missile will only embolden dictator Kim Jong-Un.
Following reports that US intelligence suggests the North might be able to pair a nuclear warhead with a missile capable of reaching targets on the United States mainland, Trump warned North Korea that "it faces retaliation with fire and fury unlike any the world has seen before".
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Mattis said the U.S. and its allies would win any arms race or conflict.
China, which is North Korea's closest ally despite its anger at Pyongyang's missile and nuclear programs, described the situation as "complex and sensitive", and urged calm and a return to talks.
Air Forces Pacific last week announced that 12 F-16s and 200 Wisconsin Air National Guardsmen would join in the Ulichi exercises later this month. His comments punctuate President Donald Trump's warning that North Korea will be met with "fire and fury" if it threatens the US.
USA secretary of state Rex Tillerson said President Trump had delivered such a stark message because the North Korean leader "doesn't seem to understand diplomatic language".
"Above all, President Moon emphasized that South Korea can never accept a war erupting again on the Korean Peninsula", his office said in a statement after the phone call. A small section of the Tumen River also forms North Korea's border with Russian Federation to the northeast. The Korean Demilitarized Zone marks the boundary between North Korea and South Korea.