Bougainville Referendum Commission Chairman Bertie Ahern was cheered when he announced that more than 98% of valid ballots favored independence. The only other option in the vote was greater autonomy from Papua New Guinea.
The referendum is nonbinding, and independence would then need to be negotiated between leaders from Bougainville and Papua New Guinea. The final say would then go to lawmakers in the Papua New Guinea Parliament. The process of becoming a separate nation could take years to achieve.
Papua New Guinea Prime Minister James Marape's office said he was out of town and was not available for comment.
Around 85% of eligible voters cast more than 181,000 ballots in two weeks of voting.
The referendum is a key part of a 2001 peace agreement that ended a civil war in which at least 15,000 people died in the cluster of islands to the east of the Papua New Guinea mainland.
The violence in Bougainville began in the late 1980s, triggered by conflict over an enormous opencast copper mine at Panguna. The mine was a huge export earner for Papua New Guinea, but many in Bougainville felt they received no benefit and resented the pollution and disruption of their traditional way of living.
The mine has remained shut since the conflict. Some believe it could provide a revenue source for Bougainville should it become independent.