The director of the Centers for Disease Control and Prevention said workers at high risk of Covid-19 infection should receive a booster of Pfizer Inc.’s vaccine, in a decision that deviated from the recommendation of an advisory panel that the CDC typically follows.

CDC Director Rochelle Walensky signed off on a series of recommendations from the panel, saying boosters should be offered to people 65 and over as well as those 50 to 64 years with underlying medical conditions, according to the CDC. People with underlying medical...

The director of the Centers for Disease Control and Prevention said workers at high risk of Covid-19 infection should receive a booster of Pfizer Inc.’s vaccine, in a decision that deviated from the recommendation of an advisory panel that the CDC typically follows.

CDC Director Rochelle Walensky signed off on a series of recommendations from the panel, saying boosters should be offered to people 65 and over as well as those 50 to 64 years with underlying medical conditions, according to the CDC. People with underlying medical conditions ages 18-49 may also get shots. The extra dose would be given at least six months after the last shot.

Underlying medical conditions warranting a booster shot are wide-ranging. The CDC said they include cancer, chronic lung and kidney disease and heart disease, as well as diabetes, obesity, pregnancy and smoking.

But one of Dr. Walensky’s endorsements went against the panel’s recommendation. She said people may be offered boosters if they are ages 18 to 64 years and are healthcare workers or have another job that puts them at increased risk of being exposed to the virus.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Dr. Walensky said in a statement late Thursday. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

She said the U.S. vaccination campaign remains focused on inoculating as many people as possible with primary doses and that the CDC would review information on the Moderna Inc. and Johnson & Johnson vaccine boosters as soon as possible.

The decision to go against the recommendation of the Advisory Committee on Immunization Practices is highly unusual, and marks the latest shift in federal planning for giving boosters. It came after the Food and Drug Administration cleared boosters of the vaccine developed by Pfizer and German partner BioNTech SE for people 65 and older and certain other adults at high risk of severe illness.

The CDC’s decision early Friday came after FDA staff and advisers refused to endorse the Biden administration’s original plan for making boosters widely available beginning this week, saying data so far didn’t support broad use.

Some health experts inside and outside the federal government have expressed concern that the back-and-forth over who should get the extra doses will confuse people and potentially deter some who would benefit from the additional dose.

The White House has said it wanted to make plans for boosters to make for a smooth rollout, but it always planned to leave the details of authorization to regulators acting on scientific evidence.

Those who qualify for boosters will have to attest to their eligibility but won’t have to provide additional documentation, CDC officials said.

The FDA authorized third Pfizer doses for people 65 years and older and adults at high risk for severe illness, including because of their jobs or where they live.

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The CDC’s Advisory Committee on Immunization Practices, or ACIP, is a 15-member panel including pediatricians, infectious-disease doctors and other medical experts.

After the FDA greenlights vaccines, the ACIP advises the CDC on who should receive them, when and under what circumstances. Usually it meets three times a year, though the panel has met many more times during the pandemic.

The FDA, in seeking to define groups of adults eligible for the vaccine in its own authorization, did some of the work that the committee usually does. The exclusion of people at risk for Covid-19 at work is likely to cause confusion and places the country in uncharted territory, experts said.

More than 26 million people who have received two doses of the Pfizer vaccine at least six months ago could potentially be eligible for a booster on Sept. 27, according to the CDC. About half are 65 and older.

The panel was worried about supporting a broad recommendation for people such as healthcare workers or others exposed because of their jobs. It feared it would essentially allow anyone who wanted a booster to get one without enough safety data to back that up.

“It seems uncharacteristically openly ended for the lack of data of need in any of these groups,” said Sarah Long, a professor of pediatrics at Drexel University College of Medicine.

—Jared S. Hopkins contributed to this article.

Write to Felicia Schwartz at felicia.schwartz@wsj.com