At the White House Friday, President Obama announced the resignation of Health and Human Services Sec. Kathleen Sebelius and nominated Office of Management and Budget Director Sylvia Mathews Burwell to take her place. (The Associated Press)

In selecting Sylvia Mathews Burwell to direct the government’s largest domestic agency, President Obama did not turn to the ranks that have often filled the post of secretary of health and human services — members of Congress, governors, experts in health policy.

After the political tumult and technical defects that have hindered the Affordable Care Act, Obama selected a trusted budget wonk with a reputation for management acumen and a rapport with lawmakers on Capitol Hill.

By choosing someone he twice called a “proven manager” in his announcement Friday, Obama signaled his need for a set of steady hands to shepherd his signature domestic initiative through the end of his tenure.

Even though the administration met a first-year insurance enrollment goal, many potential obstacles lie ahead before the health-care law is fully implemented. And in the polarized environment of midterm elections, ­every misstep becomes fodder for a 30-second political ad.

“It’s fair to say we’ve just started implementation,” said Dan Mendelson, head of the health consulting group Avalere. “One year down and two years to go.” Mendelson worked with Burwell at the Office of Management and Budget when she was its deputy director under President Bill Clinton.

In succeeding Kathleen Sebelius, Burwell instantly would become the Obama administration’s most visible champion of the law — and a lightning rod for its critics — at a time when public opinion remains deeply divided.

While Burwell, who has been the director of OMB since last year, is expected to gain Senate approval, her confirmation hearings will give Republican opponents a national platform to again attack the law.

Senate Minority Leader Mitch McConnell (R-Ky.) said he hoped Burwell’s selection “is the start of a candid conversation about Obama­care’s shortcomings and the need to protect Medicare for today’s seniors, their children and their grandchildren.”

And Kirsten Kukowski, spokeswoman for the Republican National Committee, warned Friday, “We should make the hearings a priority because it’s an opportunity to get answers about the future of health care for Americans.”

Burwell will be immersed immediately in decisions that will have a critical impact on how many Americans join the 7.5 million who have signed up for health insurance through new federal and state marketplaces under the law.

Among the pressing issues are the premiums that insurers will propose for the next insurance enrollment period, which is to begin in mid-November. The rates could be pushed up by the likelihood that fewer than expected young and healthy consumers joined health plans for 2014.

The administration is still building parts of on which insurers rely. Many Medicaid applications coming through the Web site are caught in limbo. And the enrollment portal for the small-business exchanges remains unfinished.

Meet Sylvia Burwell -- President Obama's pick for the next Health and Human Services secretary. Here is everything you need about her career in less than a minute. (Jackie Kucinich, Theresa Poulson and Jeff Simon/The Washington Post)

On top of that, several states, including Maryland and Oregon, are still trying to ensure their separate state-run insurance marketplaces are simply functional.

At HHS, Burwell would oversee a vast and multi-tentacled bureaucracy with responsibility for, among other things, drug safety, anti-poverty programs, mental health issues and biomedical research. Despite this broad set of priorities, the 2010 health-care law will inevitably dominate Burwell’s attention, health policy experts agreed.

The HHS secretary has enormous power in implementing the health-care law because Congress left much up to the secretary. For example, the law says health plans on the marketplaces must cover 10 minimum health benefits, such as maternity care and mental health treatment, but did not specify the exact terms of that minimum coverage, leaving it up to the head of HHS.

Under Sebelius, the department handed over much of that latitude to the states. As a result, some states require, for instance, coverage of in-vitro fertilization, while others do not. Burwell may choose to take a more active role in specifying coverage terms.

“Now, the question is, does the secretary try to come up with a universal definition of what is a universal health benefit?” said Timothy Jost, a professor of health law at Washington and Lee University and a consumer advocate who supports the Affordable Care Act.

And Burwell will have to tackle what advocates such as Ron Pollack, president of Families USA, say is the law’s biggest shortcoming: The fact that millions of Americans who were supposed to benefit from the law have not because their states chose not to expand Medicaid, the state-federal health-care program for the poor.

Ultimately, though, Burwell and her colleagues will be implementing the same vision — one that emanates from the White House.

“Their interpretation of the president’s agenda can, at the margin, have a significant effect on how the law is implemented,” said Ed Haislmaier, a senior research fellow at the conservative Heritage Foundation. But none will vary too far from that agenda, he added.

The decision to replace Sebelius with Burwell was so closely held that most senior White House staffers were taken by surprise when chief of staff Denis McDonough announced it at roughly 6 p.m. Thursday at their regular meeting. The group broke into applause, according to one participant, though some joked with Burwell later about her decision to take on an even more thankless task than her current post as the administration’s budget chief.

While she served on the board of MetLife and dealt with health policy in the context of her OMB posts and at the Bill & Melinda Gates Foundation, Burwell remains unknown to many federal health experts.

“I don’t think any of us know her,” said Robert Laszewski, head of Health Policy and Strategy Associates. “She’s been a budget wonk.”

Burwell has not outlined her vision for the agency she now may head, and only spoke briefly about it Friday.

“If confirmed by the Senate, I look forward to carrying on the important work of ensuring that children, families and seniors have the building blocks of healthy and productive lives, whether it’s through implementing the Affordable Care Act, supporting affordable child care, or finding new frontiers to prevent and treat disease,” she said.

Patty Stonesifer, who served as chief executive of the Gates Foundation, said Burwell’s strength lies in her ability to focus on individuals affected by public policy — like a child in Africa who lacks adequate nutrition — as well as “systems-level change” on sweeping issues such as agriculture.

“She’s very fierce for the mission when she buys on,” Stonesifer said. “She really holds tight to ‘This is what we’re supposed to be doing here,’ and she’s very focused on the ultimate outcome.”

Rep. Chris Van Hollen (Md.), the top Democrat on the House Budget Committee, said the fact that Burwell “has been able to earn people’s respect will go a long way” toward easing her confirmation. His GOP counterpart, Paul Ryan (Wis.) issued a statement calling Burwell “a consummate professional,” but added, “At HHS, she’ll have her work cut out for her.”

Sandhya Somashekhar and Jason Millman contributed to this report.