The EU will have to bounce back from one of its biggest setbacks in its 62-year history to confront an ever more complicated world with a new, staunchly free-market competitor just across the English Channel.
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Britain officially departs the EU at 11 p.m. local time Friday, midnight in Brussels (2300 GMT, 6 p.m. EST). The departure comes 3 years after the country voted by a margin of 52%-48% to walk away from the club that it had joined in 1973.
It's the first time a country has left the EU, and many in the bloc rued the day. In Brussels, EU Commission President Ursula von der Leyen lamented that "as the sun rises tomorrow a new chapter for our union of 27 will start."
But she warned Brexit day would mark a major loss for the U.K. and said the island nation is heading for a lonelier existence. "Strength does not lie in splendid isolation, but in our unique union." Newspapers across the continent were marking the departure with headlines of "Adieu to Europe" and "Bye-Bye!" next to a Union Jack flag.
U.K. Prime Minister Boris Johnson is to meet in the morning with his Cabinet in the pro-Brexit town of Sunderland, in northeast England. He is scheduled to deliver a televised address to the country an hour before departure, calling Brexit "not an end but a beginning."
According to his office, he will describe it as "a moment of real national renewal and change."
The government hopes the moment will be marked in a dignified, nontriumphalist fashion, with red, white and blue lights illuminating government buildings and a countdown clock projected onto the prime minister's 10 Downing St. residence.
Some Brexit supporters will be holding more raucous celebrations. Arch-Brexiteer Nigel Farage and his band of devotees will gather for patriotic songs and speeches in London's Parliament Square to mark a moment that even Farage sometimes doubted would ever come.
Others do not feel like indulging in any festivities. Lawyer Alice Cole-Roberts said Friday morning she expects "more and more frustration" as Brexit unfolds.
"It's a very sad day," she said. "I'm very upset that we are leaving the European Union and I simply wish it didn't happen."
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For the next 11 months, the EU and Britain will already be pitted against one another as they seek to negotiate a trade and security deal as part of their new relationship.
"It is clear that the EU will be united in defending its interests," von der Leyen said. "For all third countries, the rule is that only by recognizing the EU single market rules can you reap the rewards." Britain has already vowed it will not agree to follow an EU rule book in return for unfettered trade.
"As good friends, we can be tough and fair in negotiations," she said.
Britain was never a wholehearted EU member, but actually leaving the bloc was long considered a fringe idea. It gradually gained strength within the Conservative Party, which has a wing of fierce "euroskeptics" - opponents of EU membership. Former Prime Minister David Cameron eventually agreed to hold a referendum, saying he wanted to settle the issue once and for all.
It hasn't worked out that way. Since the 2016 vote, the U.K. has held fractious negotiations with the EU that finally, late last year, secured a deal on divorce terms. But Britain is leaving the bloc arguably as divided as it was on referendum day.
By and large, Britain's big cities voted to stay in the EU, while small towns voted to leave. England and Wales backed Brexit, while Northern Ireland and Scotland voted to remain.
In Brussels, the Brexit-backing lawmakers at the European Parliament were making the most of their last day, walking to the sound of bagpipes, with luggage in hand, to take the Eurostar high-speed train back to London.
In Edinburgh, the EU flag will not be lowered outside the Scottish Parliament on Friday night. Lawmakers there voted to keep it as a symbol of their opposition to Brexit. Scotland's pro-EU government will also light up two government buildings in the blue and yellow of the EU flag on Friday.
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Scottish Brexit Secretary Mike Russell urged the EU to "leave a light on for Scotland" so that it could eventually return. The governing Scottish National Party wants Scotland to become an independent EU member country, separate from the U.K.
"It is a stark fact that tomorrow we leave, dragged out against our will, despite the clear instruction of the Scottish people," Russell said Thursday.
London, which is home to more than 1 million EU citizens, also voted by a wide margin to stay in the bloc. Mayor Sadiq Khan, who has linked the Brexit vote to a rise in xenophobic abuse, said Britain's capital would remain "a truly global, European city."
"We continue to be a beacon for progressive ideas, for liberal values and for decency and diversity," Khan said in a statement. "And we will continue to welcome people from around the world, regardless of the color of their skin, the color of their passport or the colors of their national flag."
Britain's departure is a historic moment, but it only marks the end of the first stage of the Brexit saga. When Britons wake up on Saturday, they will notice very little change. The U.K. and the EU have given themselves an 11 month "transition period" -- in which the U.K. will continue to follow the bloc's rules -- to strike new agreements on trade, security and a host of other areas.
Negotiations are due to start in March, and the early signs are not encouraging.
Johnson's government hopes to negotiate a deal with the EU alongside a free trade agreement with the United States. That's also likely to be contentious. Opposition politicians are already raising concerns about issues ranging from food-safety standards - especially the U.S. practice of chlorine-washing chicken to kill germs - to drug prices.
U.S. Secretary of State Mike Pompeo, who met Johnson in London on Thursday, said the U.S. would put Britain "at the front of the line" in its trade relationships after Brexit.