Staged against a backdrop of shuttered banks and threats of financial apocalypse, the vote looked too close to call and may not produce the clear mandate for negotiations that Athens’ creditors seek, Reuters reported.
Greeks are split on whether to accept an offer by creditors that Prime Minister Alexis Tsipras calls a "humiliation" and is urging people to reject.
Investors and European policymakers say a rejection would set Greece on a path out of the euro, destabilizing the global economy and financial markets.
"I voted 'No' to the 'Yes' that our European partners insist I choose," said Eleni Deligainni, 43, in Athens.
"I have been jobless for nearly four years and was telling myself to be patient ...but we've had enough deprivation and unemployment."
Voting on whether to accept more taxes and pension cuts would be divisive in any nation, even at the best of times.
In Greece, the choice is faced by an angry and exhausted population who, after five years of crippling austerity, have now suffered through a week of capital controls imposed to prevent the collapse of the nation's financial system.
Pensioners besieging bank gates to claim their retirement benefits, only to leave empty-handed and in tears, have become a symbol of the nation's dramatic fall over the past decade.
Polls close at 7 p.m. (1600 GMT), with the first official projection of the result expected at 9 p.m.
Four opinion polls published on Friday showed the 'Yes' vote marginally ahead. A fifth put the 'No' camp 0.5 percentage points in front. All were well within the margin of error.