Both sides of the campaign have urged the nearly 46,499,537 registered voters, including 1.2 million British Indians, for a big turnout as Prime Minister David Cameron made his final appeal to "get out there and vote Remain" and reject the "untruths" of the camp in favour of 'Brexit' or Britain's exit from the EU.
Cameron will vote in his constituency of Witney, Oxfordshire, before returning to Downing Street to watch the results come in.
Immigration to Britain, which has risen significantly in recent years, is a key issue in the referendum that has seriously divided the country.
On the opposing side, former London mayor Boris Johnson, who is widely touted as a future prime minister, headed the final drive for the Vote Leave campaign, insisted his side was "on the verge of victory" and that today could mark the UK's "independence day".
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The referendum ballot paper asks a 'Yes' or 'No' question: "Should the United Kingdom remain a member of the European Union or leave the European Union?" and whichever side gets more than half of all votes cast is considered to have won.
The weather forecast for polling day remains mixed, with thunderstorms causing flooding in some parts of the country.
After the referendum polls close at 10 pm local time, sealed ballot boxes will be collected and transported to the count venue for each of the 382 local counting areas.
Individual areas' results will then be declared throughout
the night, along with results from 11 regional counts.
The UK's Electoral Commission estimates a final result around breakfast time tomorrow.
In a departure from the norm, no major broadcasters have commissioned any exit polls over concerns about accuracy following the fiasco of the last general elections, when a hung Parliament had been predicted wrongly instead of a big Conservative party majority.
The European Union is made up of 28 countries who have come together for trade and security.
It was originally set up as the European Economic Community (EEC) in 1958 with six members: Belgium, Germany, France, Italy, Luxembourg and the Netherlands. The EEC changed its name to the European Union (EU) in 1993. The UK had joined the EEC back in 1973.
There has only been one other UK-wide referendum on the issue of EU membership, in 1975 when the country voted to stay in the European Community.
Citizens of Ireland, Malta and Cyprus resident in the UK can vote as can Commonwealth citizens resident in the UK and Gibraltar, including Indians.