EU leaders have insisted that the UK must move swiftly to negotiate leaving the organisation, saying any delay would prolong uncertainty.
European Commission head Jean-Claude Juncker stressed the "Union of the remaining 27 members will continue".
The UK voted by 52% to 48% to leave the EU, and David Cameron has announced he will step down as PM by October.
He has said it will be up to the new PM to invoke the article that will begin the UK's withdrawal.
Global stock markets fell heavily on the news of the so-called "Brexit" and the value of the pound has also fallen dramatically.
Mr Juncker went into crisis talks with European parliament president Martin Schulz, president of the European Council Donald Tusk and Dutch PM Mark Rutte on Friday morning.
They then released a statement saying they regretted but respected the British decision.
They called for the UK "to give effect to this decision of the British people as soon as possible, however painful that process may be. Any delay would unnecessarily prolong uncertainty".
They added that the deal agreed with Mr Cameron in February to protect London's financial markets, curb immigration and opt out of closer union "ceases to exist" and "there will be no renegotiation".
Later, Mr Schulz criticised the decision by Mr Cameron and his divided Conservative party to hold the vote.
"The European Union as a whole was taken as a hostage by a party internal fight of the Tories," he said.
"And I'm not satisfied today to listen that he wants to step down only in October and once more everything is put on hold until the Tories have decided about the next prime minister. I think the European Union can't depend on internal struggles of the Tory party."
The sense of shock is palpable. EU leaders are struggling to come to terms with a huge setback for those who believe in the idea of European unity. The EU will never be the same again without the UK.
It is also clear the leaders want negotiations on a political and economic divorce to move swiftly. That means they want the UK to invoke Article 50 of the Lisbon treaty - the mechanism under which separation will be negotiated - as soon as next week, rather than wait for a new British prime minister in October.
In other words, tensions are already coming to the surface. And even though all sides are emphasising the need for co-operation, in many capitals there will be little appetite for doing the UK any favours.
The UK must now invoke Article 50 of the Lisbon Treaty to leave, which then allows for two years for withdrawal to be negotiated.
In the latest response:
German Chancellor Angela Merkel expressed "great regret" at the British decision, saying: "This is a blow to Europe and to the European unification process"
Mrs Merkel said she would meet Mr Tusk, French President Francois Hollande and Italian PM Matteo Renzi in Berlin on Monday.
Mr Hollande said the vote "seriously puts Europe to the test", adding: "I respect this painful choice. France will continue to work with this friendly country".
The European parliament has called a special session for next Tuesday to assess the vote.
Russian President Vladimir Putin said the decision showed the UK's unhappiness with migration and security.
Europe's political order has been overturned - with far-reaching consequences that no-one can accurately predict.
Article 50 of the EU Treaty
In force since 2009 but never tested
Allows governments to notify intent to leave. Talks then begin on a range of issues between the leaving nation and other EU members.
If no deal is reached, membership will automatically cease two years after notification.
The article is only a basic template for leaving, settling the date and some other matters. It does not automatically include issues such as movement of people or trade. The latter could take years to conclude.
Some EU politicians fear a domino effect from Brexit that could threaten the whole organisation.
Polish President Andrzej Duda said everything possible must be done to prevent other countries leaving.
Leaders of Eurosceptic parties in France, the Netherlands and Italy quickly demanded referendums in their own countries.
Reacting to the vote, UK Independence Party leader Nigel Farage said "the EU is dying".
But Mr Tusk said this was "not a moment for hysterical reactions".
Although many EU leaders expressed shock and dismay at the vote, they also urged solidarity and some stressed the need for change.
Estonian Prime Minister Taavi Roivas said: "We must... work hard so that we do not lose the unity of the European Union"
Portuguese President Marcelo Rebelo de Sousa said "the European project remains valid to defend the values that mark our common identity"
Czech PM Bohuslav Sobotka said: "Despite the disappointment many of us feel... we must realise that this is not the end of the world and it's absolutely not the end of the EU"
Greek PM Alexis Tsipras said the vote was "either a wake-up call or the beginning of a dangerous path", adding: "We urgently need a new vision and beginning for a united Europe"
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