Updated 5:32 a.m. ET
British voters have decisively chosen to leave the European Union, 52 percent to 48 percent.
Prime Minister David Cameron announced he will resign before his Conservative Party conference in October.
"I was absolutely clear about my belief that Britain is stronger, safer and better off inside the European Union," Cameron said Friday. "But the British people have made a very clear decision to take a different path, and as such I think the country requires fresh leadership to take it in this direction."
The results will end the United Kingdom's 43-year EU membership, though the process of leaving the 28-nation group will likely take many years.
"The EU's failing, the EU's dying," said Leave campaigner Nigel Farage after the official results were announced. Farage said he anticipates the Netherlands and Denmark will follow Great Britain out of the European Union.
The results showed sharp regional divisions in the United Kingdom. London, Scotland and Northern Ireland had strong pro-EU results, while rural and economically depressed areas backed Brexit in large numbers.
Jeremy Corbyn, leader of the opposition Labour Party, said voters were reacting to decades of mistreatment by successive governments.
"Many communities are fed up with cuts, fed up with economic dislocation and feel very angry at the way they've been betrayed and marginalized," Corbyn said.
Markets worldwide plunged as the vote counts trickled in Thursday night and Friday morning. The British pound fell to its lowest level since 1985, down almost nine percent against the U.S. dollar. Gold and the Japanese yen went up.
Current EU president Donald Tusk said the group is "determined to keep our unity at 27," referring to the number of member nations minus Great Britain. He went on to say, quoting his father, "What doesn't kill you makes you stronger."
Northern Ireland's strong Remain vote led Sinn Fein chairman Declan Kearney to call for a referendum on unification with Ireland, an EU member country. Sinn Fein is the largest Irish nationalist party in Northern Ireland.
Germany's foreign minister Frank-Walter Steinmeier tweeted the vote was "a sad day for Europe and Britain." France's foreign minister Jean-Marc Ayrault said he was "sad for the United Kingdom."