As Republican candidate Donald Trump took the lead in the results, Democrat Hillary Clinton looked uncertain to win - for the first time in the campaign.
Opinion polls before election day had given Mrs Clinton a slim lead.
But with Mr Trump's edge in many battleground states, Mrs Clinton tweeted: "This team has so much to be proud of. Whatever happens tonight, thank you for everything."
Earlier this morning, the likelihood of a Trump victory surpassed that of Mrs Clinton for the first time on The New York Times predictor. He has taken key swing states such as Florida, Ohio and North Carolina.
Mr Trump leads Mrs Clinton by 244-197 in the Electoral College votes.
He also captured conservative states in the south and midwest, while Mrs Clinton swept states on the east coast, Illinois in the midwest and California in the west.
If Mrs Clinton does win the election, she will make history by becoming the first female president of the US.
Much of the campaign has focused on the character of the candidates rather than their policies: Mrs Clinton, 69, a former US secretary of state, and Mr Trump, 70, a New York businessman and reality TV star.
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The pair often accused each other of being fundamentally unfit to lead the United States as it faces challenges such as an arduous economic recovery, Islamist militants and tensions with Russia.
While Mr Trump's candidacy has embodied an attack on America's political establishment. Mrs Clinton has represented safeguarding the political order.
A Clinton presidency would likely provide continuity from fellow Democrat Barack Obama's eight years in the White House, although if Republicans retain control of at least one chamber in Congress more years of political gridlock in Washington could ensue.
Mrs Clinton's camp was hoping that the large Latino vote could give them the edge in Florida after critics accused Mr Trump of using racist rhetoric against Mexicans and Hispanics.
Mrs Clinton is not a newcomer to campaigning, she has spent almost all of her adult life in the public eye and involved in politics.
She spent eight years in the White House as US first lady, the wife of President Bill Clinton, from 1993 to 2001 before serving as a senator and as Mr Obama's secretary of state.
She also ran for president in 2008, but lost to Mr Obama for the Democratic nomination.
However, Mrs Clinton’s campaign has not been without controversy. With a long reputation for secrecy, she sustained damaging blows from her handling of classified information as the country's top diplomat.
The FBI spent about a year investigating her use of an unauthorised private email server for her work as US secretary of state between 2009 and 2013 after it emerged that there were classified government secrets in some of her emails.
In July, the FBI characterised Mrs Clinton's handling of classified information via email as "extremely careless" but, after a months-long investigation, it recommended that no criminal charges be brought.
The email debacle arose again just last week when the FBI reopened its investigation into Mrs Clinton’s emails.
It was only two days before the election that FBI Director James Comey (above) reiterated that she would not face criminal charges.
Clintons cast their votes in New York school
Mrs Clinton voted with her husband Bill at a primary school near their home in Chappaqua, New York, earlier.
"I'm so happy, I'm just incredibly happy," said Mrs Clinton spoke to reporters as she emerged from the polling station
Mrs Clinton told reporters after casting her ballot that it was "the most humbling feeling" to vote for herself as she seeks the nation's highest office.
"I know how much responsibility goes with this and so many people are counting on the outcome of this election, what it means for our country," she added.
"And I will do the very best I can if I'm fortunate enough to win today."
