Earlier, during the flight to South Korea from Indonesia, Clinton told reporters that North Korea's leadership situation was uncertain and that the United States was worried the Stalinist country may soon face a succession crisis to replace dictator Kim Jong Il.
Clinton said the Obama administration was deeply concerned that a potential change in Pyongyang's ruling structure could raise already heightened tensions between North Korea and its neighbors as potential successors to Kim jockey for position and power.
Her comments were a rare, if not unprecedented public acknowledgment from a senior U.S. official that the secretive nation may be preparing for a leadership change following reports that Kim suffered a stroke last year.
Clinton said the South Koreans are particularly worried "about what's up in North Korea, what the succession could be, what it means for them, and they are looking for us to use our best efforts to try to get the agenda of denuclearization and nonproliferation back in gear."
"Everybody is trying to sort of read the tea leaves as to what is happening and what is likely to occur, and there is a lot of guessing going on," Clinton said, referring to talks between Chinese, South Korean, Japanese and U.S. officials about the situation in the North.
"But there is also an increasing amount of pressure because if there is a succession, even if it's a peaceful succession, that creates more uncertainty and it may also encourage behaviors that are even more provocative as a way to consolidate power within the society," she said.
Clinton's remarks came as North Korea stepped up belligerent rhetoric towards the United States and South Korea amid signs the North is planning to test fire what intelligence analysts believe is a long-range missile.
Just hours before Clinton arrived in Seoul, the North Korean military stepped up its war rhetoric Thursday, issuing a statement in which it accused South Korean president Lee Myung-bak of misusing "nonexistent nuclear and missile threats" as a pretext to invade. It also warned it was prepared for an "all-out confrontation."
The strident statement carried on state-run media comes amid reports that the North is preparing to test-fire a long-range missile.
Visiting Tokyo earlier this week,. "The possible missile launch that North Korea is talking about would be very unhelpful in moving our relationship forward," she said.
Analysts say North Korea is using the threats and missile test preparations to win President Obama's attention at a time when nuclear negotiations with the U.S., South Korea and three other nations stand at a deadlock and tensions with the South are at their highest level in a decade.
North Korea, however, said Monday it "has no need to draw anyone's attention" and has defended its right to use missiles as part of its space program.
Kim, 67, inherited leadership from his father, North Korea founder Kim Il Sung, in 1994, creating the world's first communist dynasty. He rules the nation of 23 million people with brutal authority, allowing no opposition or dissent.
His failure to show up last September for a military parade marking the country's 60th anniversary spurred questions about the health of a man believed to have diabetes, heart disease and other chronic ailments.
Citing intelligence, South Korean and U.S. officials later said Kim suffered a stroke and underwent brain surgery in August.
North Korean officials have steadfastly denied Kim was ever ill.
However, state-run media made no mention of Kim's public appearances for weeks last fall, feeding fears that his sudden death without naming a successor could spark a power vacuum, internal struggle in the nuclear-armed nation or send scores of hungry North Koreans fleeing to China.
Clinton, who will visit China over the weekend, said she would be seeking advice in Seoul and Beijing about how to resume stalled six-nation disarmament talks given questions about Kim's health and who is now or may soon be in charge in Pyongyang.
Clinton is to meet with Lee on Friday and said she would speak to him and others about how to defuse tensions between the two Koreas.
Relations between the two Koreas have been tense since Lee took office a year ago taking a harder line toward the North than his liberal predecessors.
The North's military, in a statement carried by the official Korean Central News Agency, called the Lee administration a "group of traitors" and warned it "should never forget that the (North) Korean People's Army is fully ready for an all-out confrontation."
The North's Radio Pyongyang said tensions are so high that armed skirmishes could break out near their disputed sea border at any time, according to South Korea's Yonhap news agency, which monitors the broadcasts from Seoul.
The South Korean military is prepared to repel any North Korean provocation, Gen. Kim Tae-young, chairman of the country's Joint Chiefs of Staff, reportedly told lawmakers. Officials at the Joint Chiefs of Staff and the parliament could not immediately confirm the comment.
KCNA also cited joint U.S.-South Korean military exercises as proof Thursday that Washington and Seoul are preparing to attack the North. The report warned they would pay "a high price" for such a move.
The U.S. and South Korea insist the joint exercises are purely defensive.
The Unification Ministry, which handles inter-Korean affairs, urged the North to stop escalating tensions and agree to dialogue.
"We hope her visit will be a strong message against North Korea's military aggression," said organizer Park Chan-sung.
Clinton's visit comes amid reports that North Korea has moved a Taepodong-2 missile - believed capable of reaching Alaska - to a launch site on its northeast coast.
North Korea says it bears the right to "space development" - a term the regime used in 1998 before conducting a ballistic missile test Pyongyang claims was meant to put a satellite into orbit. The North, which claims to possess atomic bombs, carried out a nuclear test blast in 2006.
Foreign Minister Yu Myung-hwan warned that any such launch would invite U.N. sanctions because it would violate a 2006 resolution banning North Korea from pursuing missile or nuclear programs.
A missile launch "would be very unhelpful in moving our relationship forward," Clinton said Tuesday in Japan.
In a promising sign, representatives from all six nations involved in the nuclear talks were to meet Thursday and Friday in Moscow to discuss promoting regional security. The meeting will be North Korea's first official with the parties since Obama's inauguration.
The halt in the disarmament process last year came amid mounting questions about North Korean leader Kim Jong Il's health. Analysts say Kim, believed to have suffered a stroke in August, wants to extract concessions from the Obama administration before handing over control of the regime to one of his sons.
Kim's youngest son, Kim Jong Un, has registered his candidacy for the March 8 parliamentary elections, Yonhap reported Thursday, citing unnamed sources in Beijing. Yonhap called the move a sign the son has been named Kim's successor.
Yonhap said last month that the son, believed to be in his 20s, was named Kim's heir apparent but the report could not be verified.