A month to the day since she was last seen on official duties when she flew back from a trip to Europe on December 7, Clinton chaired her regular weekly Monday meeting with her closest staff and advisers.
"It is a great day here in the department... secretary Clinton is back to work," State Department spokeswoman Victoria Nuland said, adding that the 75 people present at the meeting had welcomed her with a standing ovation.
Clinton, 65, suffered a blood clot to her head after a fall in December.
She now "looks fantastic, she seems to be terrific," Nuland said. "She is in the pink, literally. She's wearing a brilliant pink jacket today."
As a joke, the staff presented her with a white football helmet, with "lots of good padding" bearing the State Department's seal, and a blue football jersey printed with the words "Clinton" and "112," to signify the number of countries she has visited during her four-year tenure, Nuland said.
Deputy secretary Tom Nides presented the gift in a big box, handing it over with a warning about life in Washington being "a contact sport," according to the spokeswoman.
Clinton had first succumbed to a virulent stomach virus, but then became dehydrated and fell, suffering a concussion. Doctors say the blood clot found later in a vein behind her right ear most likely resulted from the fall.
But now the top US diplomat, who was hospitalized for three days over the New Year, was keen to "get right back to business," Nuland added.
There are still some outstanding dossiers for Clinton to deal with before she steps down as secretary of state, with veteran Senator John Kerry already tapped by President Barack Obama to replace her.
Notably, US lawmakers are expecting her to testify on the killings of four Americans, including ambassador Chris Stevens, in the September 11 attack on the US mission in Benghazi, Libya.
Nuland stressed Clinton will appear before lawmakers to discuss the findings of an internal review which faulted the State Department for grossly inadequate security, and that she would do so before stepping down.
"Let me just say that she will testify. She will testify while she is still sitting secretary of state," Nuland said.
That would mean Clinton will testify before Kerry is confirmed by the Senate as the new secretary of state. With the Senate in recess until inauguration day on January 21, it could mean she will stay on a few days longer.
Clinton has been speaking with Kerry on a daily basis since she was released from hospital last week, and the latter has also been prepping for his new job by visiting the State Department and reviewing an armful of documents.
"The Congress is not in session, the Senate's not in session, so obviously, a new secretary can't take up duties until there has been a confirmation hearing, until there has been a vote, Nuland said.
"So our expectation is that we will be able to sequence this so that she will be testify as sitting secretary, we will also have a confirmation hearing, and all of this obviously will be preparatory to a transition."
Clinton - who has flown some 956,733 miles, spending 86.8 days in a plane and 401 days total on the road according to State Department figures - is unlikely to undertake any more foreign visits as secretary of state. Her doctors have recommended her not to travel for the time being.
It was unclear whether she remained on blood thinners, which doctors have recommended to dissolve the clot that was found in the vein behind her skull and her brain.
Doctors have told AFP that normally in such cases, patients have to take the drugs for at least three months, but in Clinton's case, it could be longer as she suffered an earlier clot in her leg in 1998.
Clinton has set a new record for the number of countries visited by any secretary of state, flying on a reconfigured US Air Force Boeing 757, outfitted with a small cabin for her use.
But she has just been pipped by her predecessor, Condoleezza Rice, who traveled 1,059,247 miles during her tenure, logging 93.87 days in a plane but only visiting 85 countries.