Cambodia's Prime Minister Hun Sen opened the 10-member Association of Southeast Asian Nations (ASEAN) event.
It will expand into an East Asia Summit involving leaders from 18 countries including US President Barack Obama and the Australian Prime Minister, Julia Gillard.
The ASEAN summit comes after months of maritime tensions within the regional bloc over how to handle disputes with China over rival claims in the South China Sea.
China insists it has sovereign rights to nearly all of the sea, including waters close to the coasts of its Asian neighbours.
Vietnam, the Philippines, Malaysia and Brunei, as well as Taiwan, also have sometimes overlapping claims to the sea.
Tensions escalated this year amid complaints by the Philippines and Vietnam that China was becoming increasingly aggressive in staking its claim to the sea.
An ASEAN foreign ministers' meeting in Phnom Penh ended in July without a joint statement because of divisions over how to handle the issue.
ASEAN Secretary General Surin Pitsuwan says this time the group will present a united front to China over the issue.
"There is a good intention to push the momentum forward," Mr Surin said ahead of the talks.
ASEAN leaders are also expected to endorse a declaration they say will enshrine human right protections for the bloc's 600 million people.
However, drafts of the pact have drawn widespread criticism from human rights groups, which say it allows loopholes for governments.
Leaders will also turn their attention to violence in Burma's Rakhine state between Muslim and Buddhist communities that has left 180 people dead since June.
ASEAN chief Surin Pitsuwan says foreign ministers have already discussed the violence during Saturday's meetings.
He says leaders may voice official concern in their end-of-summit statement on Sunday.
US President Barack Obama is due to arrive in Phnom Penh on Monday after making an historic visit to Burma.
Rights groups have urged Mr Obama to raise concerns over the violence in Rakhine state.
Mr Obama's aides say he will raise "grave concerns" in Phnom Penh over Cambodia's rights record and the need for political reform when he meets Prime Minister Hun Sen.
"We'll continue to make clear that we want to see greater political freedom in Cambodia," said Ben Rhodes, a deputy US national security advisor who is travelling with Mr Obama.
ASEAN leaders are also aiming to use the Phnom Penh talks to push forward a planned giant free trade zone with China, Japan, South Korea, India, Australia and New Zealand.
Negotiations for the free trade area, which would account for roughly half the global population and around a third of the world's annual gross domestic product, are set to be officially launched on Tuesday.