A month to the day since she was last seen on official duties when she flew back from a trip to Europe, Ms 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.
Ms Clinton, 65, suffered a blood clot to her head after a fall in December.
She now "looks fantastic, she seems to be terrific," Ms Nuland said.
"She is in the pink, literally. She's wearing a brilliant pink jacket today."
She said as a joke, the staff presented Ms Clinton 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.
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 Ms Nuland.
Ms 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 hospitalised for three days over the New Year, was keen to "get right back to business," Ms Nuland added.
There are still some outstanding dossiers for Ms 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 politicians 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.
Ms Nuland stressed that Ms Clinton will appear before politicians 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," Ms Nuland said.
That would mean Ms Clinton will testify before Mr 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.
Ms Clinton - who has flown more than 1.5 million kilometres, 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.