The poll is the final step in a peace deal with the Catholic-majority country's largest Muslim rebel group.
A decades-long push to halt the violence that has claimed some 150,000 lives in the southern Philippines culminated Monday with a vote on giving the nation's Muslim minority greater control over the region.
The country's largest Muslim rebel group, the Moro Islamic Liberation Front (MILF), has been a key force in an insurgency that has been going on since the 1970s.
Turnout was heavy in core areas of the proposed Bangsamoro region, located primarily on the southern island of Mindanao, and voters are expected to back it overwhelmingly in most areas.
"I'm tired of the violence because my father is one of the victims," said 22-year-old Jembrah Abas, adding he was slain by unidentified attackers after advocating for peace. The election "is on the 20th anniversary of his death. I am so sick of the violence", she told AFP.
Roughly 2.8 million voters were being watched over by a contingent of 20,000 police and soldiers, due to fears rival insurgent groups could use violence to try to disrupt the poll.
The peace process began in the 1990s and does not include hardline Muslim pressure groups, including those aligned with the Islamic State group, which are also active in the southern Philippines.
In a frighteningly close call just as polls opened early Monday, a grenade was lobbed into a voting center entrance in the regional hub of Cotabato City, but failed to detonate.
"I was afraid, I was thinking about backing out (of voting)," said a tearful Leticia Mangharal, who was meters away from the explosive. "But this won't stop me."
The government and MILF hope that a new, stable Bangasmoro will attract investment to a region where brutal poverty and perennial bloodshed has fuelled recruitment by radical groups.
President Rodrigo Duterte, who also hails from Mindanao, has long backed the creation of an autonomous region for the island's Muslims.
Under the terms of the law which lays out the region's powers, Bangsamoro will get $950 million in development funds over the next 10 years, as well as a chunk of the tax revenue generated within its borders.
The national government will keep control over the police, though the leadership of the autonomous area will be closely involved in security matters.
Final results are expected to be released within four days of the voting, with an approval triggering the demobilization of a third of MILF's fighters, which the group says number 30,000.
A handful of smaller areas, which were not included in Monday's vote due to administrative delays, are set to vote on February 6 on whether to join the Bangsamoro.
Muslim groups have long been battling for independence or autonomy on Mindanao, which they regard as their ancestral homeland dating back to when Arab traders arrived there in the 13th century.
In fact, the new entity would enlarge and replace a similar autonomous zone in the same part of the southern Philippines, which struggled to complete development projects and was plagued by violence.
The proposed region includes the city of Marawi, which was seized by jihadists flying the black IS group flag in 2017 and who were only dislodged by a five-month battle that flattened swathes of the town.
Experts say the expanded devolution of powers to the region is one of the best opportunities in recent memory to bring down the persistently high levels of lawlessness in the Philippines' south.
However, corruption and mismanagement are perennial problems across the nation of 105 million, and doubts remain over whether resources promised for development would find their way to Bangasmoro projects.
"This is not the end of our struggle," MILF leader Murad Ebrahim told journalists at the group's sprawling base near Cotabato City, predicting victory. "This (transition to governing) is another layer of our struggle which will be more difficult because maybe our enemy will be ourselves," he said.