"This region is indispensable to our efforts to seize the opportunities and meet the challenges of the 21st century,'' Clinton told reporters aboard her plane en route to Tokyo.
Japan is Washington's top Asian ally, and economic issues are also expected to feature prominently in talks with Japanese officials.
Al Jazeera's Tony Cheng, reporting from Tokyo, said Clinton was expected to bring a message of support from the US for Japanese efforts to combat the effects of the world slowdown.
He said she would also be looking to enlist support from the world's number two economy for a combined effort to help alleviate the crisis.
On the security front, talks are also expected to focus on efforts to end North Korea's nuclear programme - an issue Clinton has said remains "the most acute challenge to stability in northeast Asia".
In her first foreign policy speech delivered before the New York-based Asia Society on Sunday, she said the US was "ready to help prevent the proliferation of nuclear weapons in Asia".
"This region is indispensable to our efforts to seize the opportunities and meet the challenges of the 21st century"
Hillary Clinton, US secretary of state.
She also warned North Korea against any "provocative action and unhelpful rhetoric'' amid signs it is preparing for a long-range missile launch.
Clinton said the Obama administration was ready to engage with North Korea - and sign a formal peace treaty ending the 1950-53 Korean War – but only after North Korea dismantles its weapons programme.
"When they move forward on presenting a verifiable and complete dismantling and complete denuclearisation, we'd have a great openness to working with them," she said.
Under a landmark deal in 2007 with the United States, China, South Korea, Japan and Russia, North Korea agreed to eliminate its nuclear programme in exchange for aid and promised diplomatic concessions.
The talks stalled late last year when North Korea objected to demands for external inspections aimed at verifying disarmament.
In Indonesia, Clinton is expected to announce she will attend the annual meeting of foreign ministers from the Association of Southeast Asian Nations (Asean) in Thailand later this year.
She is also expected to declare the administration's intention to sign the association's Treaty of Amity and Cooperation, which the previous Bush administration had declined to do.
On her final stop in China, talks are expected to focus on the global economic crisis, climate change and clean energy, North Korea and health issues.
Human rights groups have expressed worries that their concerns appear to have been sidelined by the Obama administration.
Clinton has not said whether she plans to meet any human rights activists during her stay in Beijing, but said she would attend a town hall-style meeting and a church where the subject might be raised.
"We're not going to be shying away from talking about human rights issues, but we have a very broad agenda to deal with when it comes to dealing with China," she said.