Department spokeswoman Victoria Nuland said the work crew was engaged in "routine maintenance in the mechanical area of the main State Department building" when flames broke out about 11 a.m., Politico reported.
"The fire was quickly extinguished and the main building has been reopened for normal weekend operations," Nuland said.
WRC-TV, Washington, reported the fire was put out with handheld extinguishers before emergency personnel arrived.
District fire department spokesman Lon Walls told the TV station one worker had life-threatening injuries, two others had serious, but non-life-threatening injuries the fourth sustained a knee injury falling off a ladder.
WRC-TV said officials said the crews were working on an eighth-floor air duct when the fire broke out.
The Washington Post reported Walls said the fire "appears to be accidental," though it was still under investigation.