A day after resigning from the Senate, John Kerry was sworn-in as Clinton's successor in a private ceremony late Friday.
"So it's been quite a challenging week saying goodbye to so many people and knowing that I will not have the opportunity to continue being part of this amazing team," Clinton told state department staff.
Her tenure ended on a turbulent note, as two people died in a suicide bombing outside the US Embassy in Turkey.
Clinton has said that she plans to write a memoir and remain active in efforts to expand the role of women in politics.