The UK stopped following EU rules at 23:00 CET as replacement arrangements for travel, trade, immigration and security co-operation came into force.
Boris Johnson said the UK had "freedom in our hands" and the ability to do things "differently and better" now the long Brexit process was over.
But opponents of leaving the EU maintain the country will be worse off.
Britain on Jan. 1 began a new year and life outside Europe, after leaving the bloc's single market trading rules to go it alone for the first time in nearly half a century.
Brexit, which has dominated politics on both sides of the Channel since 2016, became reality an hour before midnight, ending the U.K.'s 48-year obligation to follow Brussels' rules.
Like a separated couple still living together, Britain and the European Union spent 2020 wrangling and wondering whether they can still be friends.
On Thursday, the UK is finally moving out. At 11 p.m. London time — midnight in Brussels — Britain will economically and practically leave the the 27-nation bloc, 11 months after its formal political departure.
By way of contrast, Chinese pressure to stop Jaroslav Kubera visiting Taiwan took a more sinister turn when the Senate president keeled over from a heart attack. When his successor, Milos Vystrcil, embarked on the trip anyway in September, Beijing hoped to similarly scare Prague with threats of retaliation.
Britain's Parliament voted resoundingly on Dec. 30 to approve a trade deal with the European Union, paving the way for an orderly break with the bloc that will finally complete the U.K.'s long and divisive Brexit journey.
With just a day to spare, lawmakers in the House of Commons voted 521-73 in favor of the agreement sealed between the U.K. government and the EU last week.
The Brussels-London agreement over a trade deal and the start of the vaccination process gave the Greek stock market another boost too on Monday, with the benchmark easily clearing the 800-point bar to reach highs unseen in 10 months. As the year draws to a close, the losses observed in 2020 are gradually being reclaimed.
EU ambassadors have today approved the Brexit trade deal with the UK, ahead of the MPs vote.
The deal, hammered out on Christmas Eve ahead of implementation on January 1, has been given another green light with the unanimous approval.
It comes as MPs in Britain are preparing to vote on the deal in a special sitting of Parliament on Wednesday.