The Senate voted 65-31 for Sebelius to take the helm. She will now be sworn into office by the Obama White House.
The high-level federal official, typically front and center for public health emergencies like the swine flu outbreak, was the only remaining top post still unconfirmed nearly 100 days into the Obama presidency.
Debate over Sebelius was a bit drowned out today by pressing pig flu developments and Sen. Arlen Specter's announcement that he is switching parties, but Republicans have expressed frustration with her of late.
Specifically, they have questioned her on abortion rights, which she supports, and her veto last week of a bill in Kansas that would have placed new restrictions on late term abortions. That bill was targeted by Kansas Republicans at a specific doctor, who has given Sebelius campaign donations she did not entirely report.
"I think she's a wonderful lady," said Sen. Tom Coburn, R-Okla., today on the Senate floor. "But I think she lacks part of the moral clarity that is required to lead this nation in the future and to correct where we're off course on so many issues. Her ability from the start, the first day she's sworn in will be compromised by her position on this issue."
On the other hand, Cecile Richards, president of Planned Parenthood Federation of America, was quick to release a statement after the vote applauding her nomination.
"She is an excellent choice to lead HHS and has a proven track record of increasing access to affordable care," Richards said. "As countless women and their families struggle to afford quality health care during these difficult economic times, the need for health care reform that improves health outcomes is immediate."
Some Republicans had also opposed her nomination because of health care reform and the issue of comparative effectiveness, whereby the government studies which medical treatments work best. Some Republicans said that could lead to treatment that is found to not work in the aggregate being denied to a patient who wants it.
Just before the vote began, Sen. John Cornyn, R-Texas, said, "I am sad to say I will not be able to support Gov. Sebelius' nomination to Secretary of Health and Human Services" -- despite stating that, "Repulicans and all of us, I believe, want a new Health and Human Services secretary." Cornyn also said he was "concerned that Gov. Sebelius is not up to the challenge" of rooting out fraud, waste and abuse in the health care system.
Still, more lawmakers supported her nomination, including Sen. Mark Warner, who said the swine flu emergency makes her nomination even more pressing.
"It is essential for the health of the nation that President Obama has in place -- and the nation has in place -- a strong Secretary of Health and Human Services to make sure that our federal efforts on this potential pan pandemic are ably coordinated," he said.
Other High-Level Health Posts Vacant
On Tuesday, other key positions under the purview of HHS also remained unfilled today, including the director of the Centers for Disease Control and Prevention, the commissioner of the Food and Drug Administration, the deputy secretary of HHS and U.S. Surgeon General. Of the 20 top spots at HHS, 19 were being filled by acting career and political employees, and the 20th position is empty.
Meantime, the Obama administration was reassuring Americans it is well-equipped to deal with the virus, despite the vacancies. Homeland Security Secretary Janet Napolitano was been disseminating information about how to prevent the spread of the virus, as well as updates on the government's response.
"Our response is in no way hindered or hampered by not having a permanent secretary at HHS right now," White House press secretary Robert Gibbs said Monday.
"Philharmonics play without a conductor," a top federal health official told ABC News Monday. "There are a lot of people around who have been breathing this stuff for a long time."
Still, former HHS Secretary Michael Leavitt Monday said having top spots unfilled is "a significant deterrent to our best reaction."
"I would say it's crucial that the new administration put a priority in getting HHS fully staffed," Leavitt said. "The top 20 HHS officials are on vacation or being held by acting personnel. The secretary of HHS is the key player throughout the federal government in a pandemic or natural medical disaster. Some concentrated effort needs to be made to resolve that."
U.S. Rep. Ron Paul, in urging people not to panic, also suggested that Napolitano's involvement was unusual.
"How did the Department of Homeland Security get into the medical business?" the Texas Republican asked. "It is just totally out of control."
Sebelius was not yet cleared to lead the department, in large measure because of opposition to her pro-abortion stance. Her nomination also came late because she was Obama's second pick for the position; the president first picked former Sen. Tom Daschle, who later withdrew from consideration.
At the CDC, Dr. Richard Besser is temporarily at the helm until an official replacement for former director Julie Gerberding is selected. Besser told Americans Monday about precautions they can take to stop the spread of the virus, such as washing their hands, staying away from crowded places and staying home if they feel ill.
The FDA also lacks a permanent leader, with Joshua Sharfstein in charge until Obama's pick, Margaret Hamburg, is confirmed by the Senate. And it remains unknown who will fill the surgeon general post after Dr. Sanjay Gupta, Obama's unofficial pick for the job, withdrew from consideration.
Still, some said that while there's no doubt it would be best to have leaders in place, there is, nonetheless, a road map ready for these situations.
At George Mason University, public policy professor James Pfiffner told ABC News that career employees just below the top tier are well-equipped to confront swine flu and "have the expertise to do this."
Pfiffner also said that one potential plus side to the high-level vacancies is that without political appointees in place, "the link between the [president] and the career people is short."
On Monday, ABC News' medical consultant Dr. Tim Johnson said the public health structure is in "much better shape" now that it has learned from crises such as SARS and avian flu, even with high-level vacancies.
"I think they are rudderless in terms of making policy, dealing with the political issues that surround them, including health care reform," Johnson said. "I don't think that can be said about swine flu."
Leavitt, too, admitted that, "Those spots are occupied at this moment by some very capable people.
"Again, the thing that distinguishes a pandemic is the duration and the breadth," he added. "This is not a sprint. It becomes a marathon response, and permanent leadership is necessary."
ABC News' Lisa Stark, Brian Hartman and Jake Tapper contributed to this report.