"That enduring commitment is based on strategic interests and on shared values," said James Mattis, speaking at an annual Asian security conference in Singapore.
Mattis paraphrased former British Prime Minister Winston Churchill, after a participant asked whether or not the world was witnessing the "destruction" of a rules-based order founded by the US in the wake of World War II.
"Bear with us," Mattis said to a ballroom packed with defense ministers and military officers from at least 22 different countries.
"Once we've exhausted all possible alternatives, the Americans will do the right thing. We will still be there," he said.
Organizers of the annual Shangri-La Dialogue Asian Security Summit identified three potential flashpoints threatening stability in the region: North Korea's nuclear weapons program, China's militarization of man-made islands in the South China Sea, and violent Islamist extremism.
But as US President Donald Trump pursues his "America First" policy, there is growing concern over the future role of the US in Asia.
The US has been the strongest military power in the Asia-Pacific since World War II.
In opening remarks, Australian Prime Minister Malcolm Turnbull expressed disappointment over Trump's recent withdrawals from both the Paris Climate Accord and the Trans Pacific Partnership -- a multilateral trade deal that was supposed to bind the US economically with 12 other Asian nations.
Nonetheless, Turnbull urged fellow allies to be patient with the new US administration.
"We should take care not to rush to interpret an intent to engage on different terms as one not to engage at all," he said on Friday night.
For his part Mattis on Saturday pledged the US would stay engaged on North Korea, calling Kim Jong Un regime's missile program "a clear and present danger."
Mattis said the US commitment to defend longtime allies South Korea and Japan from any North Korean military threat was "ironclad." But he stressed that China must follow through on pledges to de-nuclearize the Korean Peninsula through pressure on Pyongyang.
"Words must be followed by actions," Mattis said.
The Trump administration has pledged to work with China on North Korea, but Trump has said the US would act unilaterally
if China did not step in.
Contradictory statements emerging from the Trump administration have made some long-time US allies apprehensive, observed a former senior US official.
"The thing your allies want is predictability, consistency and continuity," said William Cohen, who served as defense secretary in the Clinton administration.
"For me, the troubling thing is I don't know what the strategic plan of the US is," Cohen added.
"If the US and its President continue to see allies and partners as purely transactional ... that's going to put stress on relationships," said Ben Shreer, a defense analyst with the International Institute of Strategic Studies, the think-tank that organizes the defense conference.
Adding to the uncertainty is the rapid rise of China as the preeminent superpower in the region.
Speaking on an all-women panel, defense ministers from Japan, Australia and France all criticized China's claim of sovereignty over virtually all of the South China Sea.
Mattis also called Beijing's construction and militarization of artificial islands in the South China Sea examples "contempt for other nations interests" and "blatant disregard for international law."
China sent a relatively low-level military delegation to attend the security conference in Singapore.
During a question-and-answer session after his speech, one current and one former officer from China's People's Liberation Army politely challenged Mattis.
Qiyu Xu, a top official at the Army's National Defense University, asked about strengthened defense ties between the US and Taiwan, an island that Beijing views as a breakaway province from China.
"We believe in the peaceful resolution of the situation between China and Taiwan," Mattis answered.
"The One China Policy holds."