The FBI says it has new emails linked to her use of a private server when she was secretary of state.
Republican presidential rival Donald Trump said the move, announced 11 days before the election, was the “biggest political scandal since Watergate”.
The latest emails were discovered as part of a separate investigation into the estranged husband of top Clinton aide, Huma Abedin.
Devices belonging to her and Anthony Weiner, a former high-flying congressman, were seized in an investigation into whether he sent sexually explicit emails to a 15-year-old girl in North Carolina.
Mr Comey said while he did not yet know the significance of the findings, the FBI would investigate if any of the emails contained classified information.
Democrat presidential candidate Mrs Clinton said she was “confident” the investigation into the emails would not change the FBI’s original finding in July.
The FBI has already established the Democratic candidate had classified information on a private email server.