Addressing a regional forum in Indonesia amid efforts by Washington to demonstrate to its Asian allies that the United States would not be eclipsed by rising China, Clinton spoke out on a range of flashpoint regional issues.
On the South China Sea, where China's neighbours have complained of increasing aggression by Chinese naval forces, Clinton said "recent incidents" threatened "peace and stability" in the region.
"These incidents endanger the safety of life at sea, escalate tensions, undermine freedom of navigation, and pose risks to lawful unimpeded commerce and economic development," she told foreign ministers from the Asia Pacific.
In her prepared remarks to the ASEAN Regional Forum, Clinton also said the United States was "encouraged" by rare and unexpected meetings between senior officials from North and South Korea this week in Bali.
The contacts offered hope that the rivals may be starting to mend ties after more than a year of high tensions, which included the North's shelling of a South Korean island and alleged torpedoing of a South Korean warship.
They also raised the prospect that a compromise could be reached allowing for a re-start of the six-nation talks that are aimed at convincing the North to abandon its nuclear programme.
But Clinton put the onus on the North for any resumption of the talks, saying it had to end "provocative actions".