The deal grants largely Muslim areas of the southern Mindanao region greater political autonomy in exchange for an end to armed rebellion, but it will not end all violence in a part of the country long-plagued by lawlessness, poverty and Islamist insurgency.
Other insurgent groups have vowed to keep fighting for full independence. The region is also home to the Abu Sayyaf, a Muslim extremist network with international links that the Philippine army is battling with American support.
Malaysian Prime Minister Najib Razak, whose country brokered the peace talks, attended the ceremony.
"In signing this agreement, the two sides have looked not to the problems of the past, but to the promise of the future," Najib said.
"After so many years of conflict, and so many lives lost, it is a momentous act of courage." The peace accord concludes formal negotiations that began in 2001. A cease-fire agreement had been in place since 1997 and has been largely observed by both sides.
Previous presidents, including Corazon Aquino, Aquino's mother, tried but failed to resolve the conflict, which has stunted growth in the region and helped foster Islamic extremism in the country and elsewhere in Southeast Asia.
Much work remains to ensure that the terms of the deal and the political framework it envisages are implemented fully during the remainder of Aquino's term, which ends in 2016.
An existing five-province Muslim autonomous region is to be replaced by a more powerful, better-funded and potentially larger region to be called Bangsamoro.
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