The outgoing secretary of State, 65, was admitted Sunday to Presbyterian Hospital in New York City.
Doctors believe the current clot is related to Clinton's recent concussion, which she sustained after fainting while suffering from a stomach virus.
The diagnosis came during a follow-up exam Sunday related to that injury, according to the State Department.
Spokesman Philippe Reines said that doctors plan to monitor Clinton for 48 hours to determine if "further action is required." She is being treated with anti-coagulants.
Blood clots prompt pain and swelling and can cause heart attack or stroke depending on their movement within the body.
Some experts speculated Sunday that Clinton's clot may have resulted from her period of bed rest following the concussion, which happened in mid-December in her Washington, D.C. home.
"When you're not moving around, you don't have as much circulation in your lower extremities, and the blood sits around in your legs longer than usual," Cam Patterson, a cardiologist at the University of North Carolina-Chapel Hill told USA Today.
"That just makes it more likely that it's going to clot. If blood is moving around rapidly because someone is active, that's less likely."