The Republican nominee's projected victory came down to a handful of key swing states, despite months of polling that favoured Mrs Clinton.
The battlegrounds of Florida, Ohio and North Carolina cleared the way for his Brexit-style upset.
The hotel developer who became president
Mr Trump's victory in Wisconsin put him over the 270 out of 538 electoral college votes needed to win the White House.
The US president-elect took to the stage at his victory rally in New York and said: "I just received a call from Secretary Clinton. She congratulated us on our victory."
Media captionTears at Clinton HQ, cheers at Trump HQ
"Hillary has worked very long and very hard over a long period of time, and we owe her a major debt of gratitude for her service to our country."
He added: "It is time for us to come together as one united people."
The real estate tycoon, former reality TV star and political newcomer, who was universally ridiculed when he declared his candidacy in June last year, said his victory had been "tough".
Mrs Clinton, 69, who dreamed of becoming the first female US president, did not show up for what was meant to be her victory rally across town in Manhattan.
The mood was dark at her election night party in the Javits Center, as supporters wept and left early.
At Trump headquarters earlier, his fans cheered and chanted about the Democratic nominee: "Lock her up!"
Democrats were also unable to wrest control of the Senate from Republicans, who retained their majority in both chambers of Congress.
Media captionUS election: Relive the wild ride in 170 seconds
Hours after polling stations closed, Mrs Clinton also suffered major blows in Democratic-leaning states like Pennsylvania and Iowa, where a Republican has not won since 2004.
New Hampshire and Michigan - which were meant to be part of the Clinton firewall - remained too close to call as of Wednesday morning.
Mr Trump, a populist billionaire, provoked controversy on the campaign trail for comments about women, Muslims and a plan to build a wall along the US-Mexican border.
Mrs Clinton saw her campaign dogged by FBI investigations into whether she abused state secrets by operating a private email server during her time as US secretary of state.
Last Sunday, the law enforcement bureau cleared her once again of any criminality.
Mr Trump and Mrs Clinton were vying to succeed Democratic President Barack Obama.
After two four-year terms in the White House, he was barred by the US constitution from running for re-election.