Hillary Clinton, still in hospital early on New Year's Day, was admitted to the New York Presbyterian Hospital on Sunday following the discovery, and is being treated with blood thinners to dissolve the clot.
Doctors said she will be released once the medication dose has been established.
A routine scan revealed "that a right transverse sinus venous thrombosis had formed," doctors Lisa Bardack, of Mount Kisco Medical Group and Gigi El-Bayoumi, of George Washington University, said. They described it as "a clot in the vein that is situated in the space between the brain and the skull behind the right ear."
But they were also quick to offer reassurances saying in their statement that "it did not result in a stroke, or neurological damage."
They added: "In all other aspects of her recovery, the secretary is making excellent progress and we are confident she will make a full recovery. She is in good spirits, engaging with her doctors, her family, and her staff."
The globe-trotting diplomat has not been seen in public since succumbing to a stomach virus on returning from a trip to Europe on December 7, which forced her to cancel a planned visit to North Africa.
It's a rare absence for the most popular member of President Barack Obama's cabinet, who has been a highly visible and loyal supporter of his foreign policy agenda, traveling almost a million miles in her four years in office.
A Gallup poll released Monday showed Clinton again topping an annual list of the woman most admired by Americans, winning support from 21 percent of those surveyed. It is the 17th time she has topped the list, a landmark for Gallup.
But Clinton, 65, has made it clear she intends to step down in the coming weeks, once Senator John Kerry, tapped by President Barack Obama to replace her, is confirmed by the Senate. Clinton first fell ill with the bad stomach bug on her return from her trip, causing her to become dehydrated. She fainted and suffered a concussion.
Dr Neeraj Badjatia, chief of neurological critical care at the R. Adams Cowley Shock and Trauma Center at the University of Maryland Medical Center, told AFP a clot in the head was "not common," stressing however he was not involved in Clinton's treatment.
While Clinton's doctors have said she has not suffered any stroke or neurological damage, Badjatia said "because it is a type of blockage of a blood vessel in the brain, it is what we consider a type of stroke, and one of the rarest types of stroke we have."
"It's a very unusual form, and... it's an unusual complication of a mild head injury," he explained, adding it was hard to estimate the incidence of such clots as "it's found when you are looking for it ... many times it's diagnosed by happenstance."
Badjatia highlighted that there is also "significant monitoring" by doctors of patients prescribed anti-coagulants, and the secretary may need to be on the drugs for at least three months. It is not the first health scare for Clinton, who suffered a blood clot in her leg in 1998 when she was first lady.
Though once seen as a deeply divisive figure, she now has approval ratings above 60 percent. And many believe she will run again for the White House in 2016, despite being narrowly defeated by Obama for the Democratic nomination in 2008.
It is possible however that her health could become an issue in any White House bid, as she would mark her 70th birthday in her first year in office.
Clinton's lengthy absence from public life had sparked claims from some of her fiercest critics that she was faking illness to avoid testifying before lawmakers investigating a deadly attack on a US mission in Libya.
The September 11 assault on the US mission in eastern Benghazi, in which the US ambassador and three other American officials were killed, sparked a political firestorm in the United States.
A subsequent State Department inquiry found security at the compound was "grossly inadequate."
A separate report released Monday by the Senate homeland security committee slammed the State Department for making a "grievous mistake" in refusing to shut the mission down.