"As Secretary of State [Rex] Tillerson has made clear, our goal is not war but rather the complete, verifiable and irreversible denuclearization of the Korean peninsula," Mattis said, according to South Korea's Yonhap news agency.
Describing the government of North Korean leader Kim Jong Un as an "oppressive regime," Mattis drew contrasts with the "stark differences" in South Korea, which he said is home to a thriving democracy and free society.
North Korean soldiers across the border looked on as Mattis spoke, the report said.
South Korean Defence Minister Song Young Moo, standing beside Mattis, said Pyongyang's development of nuclear and ballistic missiles is not worth the effort since they are "weapons that can't be used."
"If it does [use them], it will face retaliation by the strong combined force of South Korea and the US," Song said.
Song urged Pyongyang to return to inter-Korean dialogue as quickly as possible, saying that "all dialogue is in a state of being severed."
Mattis arrived in South Korea on Friday morning, a day ahead of annual ministerial talks that will include the ongoing crisis with North Korea.
On Saturday, Song and Mattis will take part in talks that will see the two allies discuss further steps in the stand-off with North Korean leader Kim Jong Un and how the rogue nation can be brought into line.
The highest-ranking military officers of South Korea and the US, Jeong Kyeong Doo and Joseph Dunford, also held talks in Seoul on "key alliance issues" on Friday, Yonhap reported.
North Korea threatened in August to fire missiles into waters near Guam, a US territory, prompting Trump to threaten to rain "fire and fury" on the reclusive nation.
North Korea's nuclear tests and ballistic missile launches have resulted in international condemnation and a tightening of economic sanctions issued by the United Nations.
Next week, Trump plans to visit Asia. After a stop in Japan, the US president is expected in South Korea on November 7.
US Secretary of Defense James Mattis (L) arrives at the Joint Security Area (JSA) on the Demilitarized Zone (DMZ) in the border village of Panmunjom in Paju, which divides the two Koreas.
The US does not seek war with North Korea but instead the dismantling of Pyongyang's nuclear weapons programme, US Defence Secretary James Mattis said Friday in a brief address at Panmunjom village inside the Demilitarized Zone (DMZ).
