Speaking in the Japanese capital at the outset of a three-nation Asian trip, Clinton said the U.S., Japan, South Korea and China are consulting on an appropriate reaction to an international investigation that blamed North Korea for the incident.
She said the report proves a North Korean sub fired a torpedo that sank the ship, the Cheonan, in March and that it could no longer be "business as usual" in dealing with the matter.
While it was "premature" to discuss exact options or actions that will be taken in response, Clinton said it was "important to send a clear message to North Korea that provocative actions have consequences."
"The evidence is overwhelming and condemning. The torpedo that sunk the Cheonan ... was fired by a North Korean submarine," she told reporters at a joint press conference with Japanese Foreign Minister Katsuya Okada.
"We cannot allow this attack on South Korea to go unanswered by the international community," she said. "This will not be and cannot be business as usual. There must be an international, not just a regional, but an international response."
North Korea denies it was responsible for the sinking and has threatened to retaliate against any attempt to punish it with "all-out war."
Clinton's Asian tour, which will also take her to China and South Korea, was supposed to focus on U.S.-China economic issues. But that was before she left Washington and Thursday's release of the report that concluded that a North Korean sub had torpedoed a South Korean corvette on March 26, splitting the vessel in two and killing 46 sailors.
Input from the three countries will be key to determining an appropriate response, especially with fears that too tough a reaction could provoke new hostilities or spark chaos in the region. The Obama administration has said it wants South Korea to lead the way in coming up with possible responses.
Underscoring the concern, U.S. officials have refused to call the North's attack on the ship an act of war or state-sponsored terror, warning that an overreaction could cause the Korean peninsula to "explode."
U.S. officials said they would explore diplomatic steps through the U.N. or increase Washington's unilateral sanctions against North Korea's Soviet-style state.
At an emergency national security meeting Friday in Seoul, South Korean President Lee Myung-bak said his country was caught in a "perfect military ambush" but called for a cautious response to the sinking. Lee said the attack violated the U.N. Charter as well as the truce that ended the fighting in the 1950-53 Korean War.
Clinton's main task during her time in Beijing may be trying to persuade the Chinese to support U.N. Security Council action against North Korea. The Chinese have the most leverage over the reclusive regime, and Beijing's support for any international response to Pyongyang will be critical to its success.
Chinese officials have appealed for calm. Vice Foreign Minister Cui Tiankai called the sinking "unfortunate." But he stopped short of backing Seoul in the growing dispute, instead reiterating China's long-standing views on the need to maintain peace on the peninsula.
Clinton said Tokyo and Washington were seeking to resolve a dispute over the relocation of a key Marine base on the southern island of Okinawa by the end-of-May deadline that Japan's prime minister has set.
The Tokyo government has said it would like to move Futenma Marine air field off the island, which already hosts more than half the 47,000 U.S. troops stationed in Japan, but hasn't found a suitable alternative.
"We both seek an arrangement that is operationally viable and politically sustainable. The goal of our governments remains unchanged. We want to maintain the security of Japan and the stability of the region," Clinton said.
"We have committed to redoubling our efforts to meet the deadline that has been announced by the Japanese government."
Okada, the foreign minister, said the two sides were working together and that Tokyo would "make the utmost efforts to gain the understanding of the Okinawan people."