The referendum asks whether to recognise Indigenous people and establish a representative body that can provide non-binding advice to parliament.
This is how it will play out.
HOW DO AUSTRALIANS VOTE?
A record 17,676,347 people are enrolled to vote, an estimated 97.7% of the eligible population, the Australian Electoral Commission (AEC) said. Voting in elections and referendums is compulsory for those enrolled.
Roughly a quarter of those have already voted in early polling centres across the country, according to the Australian Electoral Commission figures on Thursday.
Another 2 million have applied to vote via post, and around 125,000 have voted via mobile polling teams.
Australians overseas have been able to vote at most of the country's embassies, consulates and high commissions, the AEC said.
Come Saturday, the rest will line up from 8 a.m. (2100 GMT Friday) at more than 7,000 polling stations set up in churches, schools and community centres across the country. Polling stations are listed here.
WHAT NEEDS TO HAPPEN FOR THE REFERENDUM TO PASS?
Referendums are notoriously difficult to pass and only eight out of 44 have done so since Australia became a country in 1901.
Success requires a double majority: a majority of voters nationwide and majorities in at least four of Australia's six states.
As it stands, such an outcome is unlikely on Saturday. Opinion polls point to a loss for the "yes" campaign.
WHEN WILL AUSTRALIA KNOW THE RESULT?
The result will be known relatively quickly compared to a political election. The simple yes/no in a referendum speeds up counting, unlike elections where voters can rank their ballots.
Western Australia is the last state where polls will close, at 6 p.m. (1000 GMT), three hours after they have closed in the eastern states of New South Wales, Victoria and Tasmania.
If voting trends are clear in the eastern states, a result may be apparent before voting has finished in Western Australia.
Prime Minister Anthony Albanese is expected to address the nation on Saturday night.
