Citizens clutched umbrellas as they lined up at the polls despite heavy rain and overnight thunderstorms causing flooding in parts of London and southeastern England.
Weather across the rest of the region was mixed — sunshine was forecast in parts of Scotland while heavy showers were set to move across Northern Ireland.
CNN crews reported brisk voting, and members of the public posted photographs of busy polling stations across the country.
A record number of people — almost 46.5 million — are registered to take part in the once-in-a generation vote.
The registered voters include Britons from England, Wales, Scotland, Northern Ireland and Gibraltar — a British territory off the southern coast of Spain.
They included UK Prime Minister David Cameron, who voted at a hall in London alongside his wife, Samantha Cameron.
British citizens living abroad have already cast their votes by mail.
Some schools across the UK are closed for the day, to serve as polling stations, but it is class as usual for others.
Polling stations across the UK will close at 10 p.m. (5 p.m. ET), with the first results expected about midnight (7 p.m. ET).
Strict rules mean that broadcasters, such as CNN, are limited in what they can report while polls are open.
The final, nationwide result is expected to be announced Friday morning.
The UK has been a member of the European Union (and its precursors) since 1973.
European citizens living in the UK are not eligible to vote unless they’re from Malta or Cyprus — both members of the Commonwealth, while citizens of the Republic of Ireland are eligible to vote if they live in the UK.
Members of Britain’s House of Lords are also eligible to vote — even if they cannot cast ballots in general elections.
Once the results are in, they will be announced by region rather than by constituency. The 12 regions comprise Scotland, Northern Ireland, Wales, London and eight English regions.