Members voted 67-28 to invoke cloture, easily getting the votes needed to avoid a filibuster and positioning her for final confirmation this week.
Burwell, who was confirmed unanimously to serve as director of the Office of Management and Budget last year, sailed through her nomination hearings in the Senate Finance and Health, Education, Labor and Pensions committees.
Even with the glowing recommendations of Republican Sens. Tom Coburn of Oklahoma, Richard Burr of North Carolina and John McCain of Arizona testifying on her behalf, Wednesday's vote was not as clear cut.
Still, Burwell's final confirmation, set for Thursday, is expected to pass easily.