The probe had been thought finished in July, when the FBI recommended that no charges be filed against Clinton.
The 69-year-old Democratic candidate -- vying to become America's first female president -- is still the frontrunner to win the November 8 election over her Republican rival Donald Trump.
Clinton has a clear lead in the polls, and voting has already begun in 34 of 50 states to choose a successor to President Barack Obama, who will hit the campaign trail again next week in defense of his onetime secretary of state.
But her momentum was threatened Friday by a renewed eruption in a scandal that has long dogged her in the race: investigations into her use of a private email server while at the State Department.
Trump gleefully seized on news that FBI agents are investigating a newly discovered group of mails sent to Clinton's private address, to see if they exposed any US secrets.
The probe had been thought finished in July, when the Federal Bureau of Investigation had recommended that no charges be filed against Clinton, though it found her to have been "extremely careless" in her use of a private server.
But FBI Director James Comey's letter to US lawmakers announcing that inquiries had been renewed shocked the campaign and rocked world markets.
Clinton cried foul, demanding that Comey reveal more information about the probe, and declared herself "confident" that voters, and the FBI, would conclude that she had done nothing wrong.
"The American people deserve to get the full and complete facts immediately," she said. "We don't know the facts, which is why we are calling on the FBI to release all the information that it has."
Her defiant words came after Trump -- himself dogged by scandal over his alleged sexual misconduct -- made hay, declaring Clinton unfit for office as a jubilant crowd of supporters in New Hampshire chanted: "Lock her up!"
Concern that the renewed probe would damage Clinton's formerly impressive momentum spooked the markets, with US stocks, the dollar and oil prices tumbling lower on the prospect of a close vote.
Comey dropped his bombshell in a letter to lawmakers, revealing that "in connection with an unrelated case, the FBI has learned of the existence of emails that appear to be pertinent to the investigation."
The FBI will thus take "appropriate investigative steps" to decide whether the new batch contains classified information "as well as to assess their importance to the investigation," he wrote.
Clinton's campaign was outraged and implied that Comey's intervention could be politically-tinged because, in Clinton's words, the letter was only sent to "Republican members of the House."
"We have not been contacted by anyone," she complained.
Clinton noted that Comey had said he himself does not know whether the emails are significant or not.
"I'm confident, whatever they are, they will not change the conclusion reached in July," she added.
According to the New York Times, the newly discovered mails emerged after agents seized electronic devices used by Clinton's closest aide, Huma Abedin, and her husband, Anthony Weiner.
Weiner, a Democratic former congressman who resigned in 2011 after he was exposed for sending explicit online messages, is under investigation over allegations he sent sexual messages to a 15-year-old girl.
According to NBC News, the newly discovered emails were sent by Abedin to Clinton from a laptop used by Weiner, who also saw a bid to become mayor of New York founder over similar claims in 2013.
Officials in Obama's administration said they had only learned of Comey's letter in news reports.
"I don't think anything has surfaced to change the president's opinions and views," White House spokesman Eric Schultz said.
Meanwhile, Trump, trailing in polls both nationally and in the swing states he must win to secure the White House, seized triumphantly on the news.
"We must not let her take her criminal scheme into the Oval Office," the 70-year-old billionaire told cheering crowds at a campaign rally in Manchester, New Hampshire.
"I have great respect for the fact that the FBI and the Department of Justice are now willing to have the courage to right the horrible mistake that they made," he added.
The news took the shine off what should have been a good day for Clinton, with the Obama administration announcing stronger than expected economic growth numbers.
On Saturday, Clinton was due to campaign in Miami in the most important potential swing state in terms of electoral votes, Florida.
Trump was due to make stops in Colorado and Arizona before heading to Nevada for a Sunday rally in Las Vegas.
Next week, both candidates will continue to barnstorm battleground states.
Trump's campaign was rocked this month by the release of 2005 footage showing him bragging about his groping women, followed by a string of accusations of sexual misconduct -- which he denies.
As he faltered, Trump piled on the defiant rhetoric, claiming the allegations were part of a plot to rig the election, and threatening not to recognize the outcome if he loses.