Voters in England have led the UK's way out of the European Union with nine areas seeing more than 70% opting to leave.
While Scotland and Northern Ireland backed staying, every English region except London voted to leave.
The England vote was 53.4% for Leave and 46.6% for Remain.
Boroughs on or near England's east coast delivered the biggest wins for Leave, with Boston in Lincolnshire recording the highest Leave percentage.
Big cities were split with Birmingham, Nottingham and Sheffield all seeing winning margins for Leave of just a few thousand.
The Church of England said it was now time for the United Kingdom to "re-imagine" its place in the world.
In a joint statement, Archbishop of Canterbury Justin Welby and Archbishop of York John Sentamu said: "As citizens of the United Kingdom, whatever our views during the referendum campaign, we must now unite in a common task to build a generous and forward looking country, contributing to human flourishing around the world.
"We must remain hospitable and compassionate, builders of bridges and not barriers. Many of those living among us and alongside us as neighbours, friends and work colleagues come from overseas and some will feel a deep sense of insecurity. We must respond by offering reassurance, by cherishing our wonderfully diverse society, and by affirming the unique contribution of each and every one."
Scottish First Minister Nicola Sturgeon said a second independence referendum north of the border was now "on the table" after Scotland had been taken out of the EU "against its will". Derby South MP Margaret Beckett, a former Labour foreign secretary, said she would be "very, very relieved but really, very surprised" if the country remained united in five or 10 years' time.
Boston saw 75.6% of voters back withdrawing from the EU while neighbouring South Holland backed Leave by 73.6%.
Boston and Skegness Conservative MP Matt Warman, who wanted to remain in the EU, said: "Britain has decided to gamble on Brexit - while I personally took the view that it wasn't a risk I wanted to take, I've also said it was one person one vote, and a gamble that could pay off.
"The government now has a duty to make sure exit negotiations with Europe are as painless as possible."
Prime minister David Cameron announced he will stand down by October. Voters in Oxfordshire, where he represents the constituency of Witney, had backed his pro-Remain stance.
Leave polled 15,188,406 votes while Remain had 13,266,996 in England. It meant the majority for Leave was 1,921,410 in England, compared with a UK-wide majority of 1,269,501.
Turnout across England was 73% with 28.4 million ballots cast.
Chiltern in Buckinghamshire had the highest turnout in England - 83.5% - and Remain won by 55% to 45%.
The lowest turnout was in Newham in London where 59.2% of registered voters cast a ballot.
Nine of the 10 areas with the highest turnouts voted to Remain in the EU.
'Roar of defiance'
The strong support for leaving along the east coast compares with just 21.4% in the London borough of Lambeth and 21.5% in Hackney.
Diane Abbott, Labour MP for Hackney, who campaigned for Remain, said the vote was a "a roar of defiance against the Westminster elite".
"We have to listen very carefully to what they were trying to say to us," she added.
The capital backed Remain most strongly in England.
Hammersmith and Fulham Council Leader, Councillor Stephen Cowan, said he wanted to send a warm message to EU citizens living in the borough.
"We are deeply grateful for the businesses they've started, the hard work they do, and for how our culture has been enriched because they have chosen to live with us in our beautiful corner of west London," he said. "We will do everything we can to ensure all of the borough's EU residents feel as welcome today, and each day thereafter, as they did yesterday."
The referendum exposed deeply divided opinion with several cities coming within a few thousand ballot papers of recording a different result.
In Leeds 50.3% voted for Remain, winning with a majority of just 2,389 votes.
Birmingham, where Labour's most prominent Leave campaigner Gisela Stuart is MP for Edgbaston, opted to withdraw by a majority of 0.8%, with 227,251 votes compared with 223,451 for Remain.
Ms Stuart said there was a responsibility to act "in the best long-term interests of this country".
Speaking at the Electoral Commission's main counting centre in Manchester, the Vote Leave chairman said the Brexit vote was "our opportunity to take back control of a whole area of democratic decisions".
All political leaders should now "reflect on whether they have accurately gauged the people's desire to govern themselves", she said.
The German-born MP said a calm cross-party effort was now needed to implement the voters' decision "in the best long-term interests of this country". And she broke into her native tongue to assure other EU nations that Britain would remain an "open, welcoming" country which would continue to co-operate with its former partners.
In Cheshire West and Chester, part of which is covered by Chancellor George Osborne's Tatton constituency, the result was 50.7% for Leave. The result was slightly more pronounced in Cheshire East, with 51.2% for Leave.
Former London Mayor Boris Johnson's constituents in Uxbridge and South Ruislip voted mostly for Leave. The constituency comes under the London borough of Hillingdon. Labour leader Jeremy Corbyn's constituents in Islington voted clearly in favour of Remain.
Reaction to the result has been as divided as the vote itself.
Dan Baker, aged 19, is studying for an undergraduate degree at the University of London Institute in Paris, and has lived in the French capital for a year.
Mr Baker, originally from Doncaster, said: "I am really disappointed, it's really sad to see England succumb to ignorance.
"I worry about myself living in Paris, my life is very European. It makes me wonder if I will be able to stay here if I want to after I have finished my studies."
However, UKIP MEP for the West Midlands James Carver said the result showed towns and cities were taking control for themselves.
Speaking about the Birmingham vote going in favour of Leave, he said: "The city of a thousand traders said 'yeah, the world's bigger than the EU'."
The city voted Leave by just 3,800 more than Remain.
Conservative leader of the House of Commons, Chris Grayling, stressed the UK would still be on good terms with the EU.
The Leave campaigner said: "We need to be an outward facing country, we're going to stay good friends and neighbours with our European partners but we're going to be internationalists, and not little Englanders."
The Local Government Association, which represents councils, said the Government would need to guarantee £5.3bn of funding allocated through EU regeneration programmes up to 2020.
A spokesman said: "EU laws and regulations impact on many council services, such as waste, employment, health and safety, consumer protection and trading and environmental standards.
"There cannot be an assumption that power over these services is simply transferred from Brussels to Westminster. If services are delivered locally, then the power over how to run them should rest locally too. Decades of centralised control over funding and services has distanced our residents from the decisions that affect their everyday lives. With greater control in our areas we can improve services and save money."