Clinton called Trump in the early morning hours on Wednesday to congratulate him on his victory, bringing a stunning end to a campaign that appeared poised right up until Election Day to make her the first woman elected U.S. president.
Trump's triumph will end eight years of the Democrat's dominance of the White House. He will also walk into the Oval Office as Republicans assume full control of the U.S. Senate and House.
With the Republicans controlling the Senate, Trump will have greater leeway in appointing a new Supreme Court justice, which could shift the bench to the right for decades.
The Republican faces a country deeply divided following a sometimes vicious presidential campaign against Clinton. Trump also faces fractures within his own party given the numerous Republicans who either tepidly supported his nomination or never backed him at all.
As he claimed victory, Trump urged Americans to "come together as one united people."
"For those who have chosen not to support me in the past, of which there were a few people, I'm reaching out to you for your guidance and your help so we can work together and unify our great country," Trump told supporters at a New York City hotel near his Trump Tower campaign headquarters, vowing to unify a deeply divided nation.
MORE: Watch Donald Trump's full victory speech
Clinton, who did not make a public appearance until Wednesday morning, urged her supporters to give Trump a chance.
"We owe him an open mind and a chance to lead," she said.
WATCH: Hillary Clinton supporters stunned by Trump victory
Trump sealed his win with decisive victories in key battleground states, including Florida, Ohio, North Carolina and others.
The Republican also won Pennsylvania and Wisconsin, states that hadn't voted for a GOP presidential candidate since the 1980s.
While Trump won the electoral vote, Clinton appeared to have won the nationwide popular vote.
Global stock markets and U.S. stock futures plunged early Wednesday, but later recovered, reflecting investor concern over what a Trump presidency might mean. The Dow Jones industrial average was flat after trading opened Wednesday.
President Barack Obama called Trump to congratulate him on his victory and extended an invitation to the Republican, asking him to meet with him at the White House on Thursday to discuss the transition.
"It is no secret that the president elect and I have some pretty significant differences," Obama said on Wednesday. "But remember, eight years ago, President Bush and I had some pretty significant differences. But President Bush's team could not have been more professional or more gracious in making sure we had a smooth transition so that we could hit the ground running."
White House spokesman Josh Earnest said Obama also called Clinton to convey his admiration for the "strong campaign she waged throughout the country."
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A New York real estate developer who lives in a Manhattan high-rise, Trump forged a striking connection with white, working class Americans who felt left behind in a changing economy and diversifying country.
He cast immigration, both from Latin America and the Middle East, as the root of problems plaguing many Americans and tapped into fears of terrorism emanating at home and abroad.
For complete election results, click here.
The Associated Press and ABC News contributed to this report.