“This is not a decision we at C.D.C. have made lightly. This weighs heavily on me,” Dr. Rochelle P. Walensky, the agency’s director, said at a news briefing on Tuesday.

Here’s what we know:

Masks in regions seeing case surges and in schools

The C.D.C. has long recommended that unvaccinated people wear masks indoors. But Tuesday’s regulations mean that even people who have been completely inoculated will once again need to mask up in public indoor spaces in parts of the country where the virus is ascendant.

In schools, health officials now recommended universal masking, regardless of vaccination status and community transmission of the virus, and additional precautions for staff, students and visitors. But they should still plan on returning to in-person learning in the fall.

How this will play out in states that have prohibited mask mandates in schools remains to be seen as well as communities where people may be weary of wearing masks.

Some states immediately adopted the new guidelines, including Illinois. The state’s public health director, Dr. Ngozi Ezike, said that despite the effectiveness of current vaccines, “we are still seeing the virus rapidly spread among the unvaccinated.”

“The risk is greater for everyone if we do not stop the ongoing spread of the virus and the Delta variant,” she said.

Gov. Steve Sisolak of Nevada followed suit on Tuesday. Starting Friday, Nevada residents in counties with high rates of transmission will be required to wear masks in public indoor spaces, regardless of vaccination status. The mandate includes Clark County, home to Las Vegas.

The C.D.C. said Americans should resume wearing masks in areas where there are more than 50 new infections per 100,000 residents over the previous seven days, or more than 8 percent of tests are positive for infection over that period.

Health officials should reassess these figures weekly and change local restrictions accordingly, the agency said. By those criteria, all residents of Florida, Arkansas and Louisiana, for example, should wear masks indoors. Nearly two-thirds of U.S. counties qualify, many concentrated in the South.

The C.D.C.’s director and other officials speak out

“The Delta variant is showing every day its willingness to outsmart us,” Dr. Walensky said at the news briefing. “In rare occasions, some vaccinated people infected with a Delta variant after vaccination may be contagious and spread the virus to others.”

Data from several states and other countries show that the variant behaves differently from previous versions of the coronavirus, she added: “This new science is worrisome and unfortunately warrants an update to our recommendation.”

In the past, Dr. Walensky has said the nation is in a “pandemic of the unvaccinated” — a point she reiterated on Tuesday. But she also said that she is concerned that vaccinated people with breakthrough infections might pass the virus on to unvaccinated family members or people with weakened immune systems.

With the earlier Alpha variant officials did not believe a vaccinated person could transmit the virus, she said.

Dr. Anthony S. Fauci, the Biden administration’s top pandemic adviser, said the C.D.C. is correct to revisit its recommendations as the virus evolves, he said.

“I don’t think you can say that this is just flip-flopping back and forth,” he said. “They’re dealing with new information that the science is providing.”

But that was before the arrival of the Delta variant, which now accounts for the bulk of infections in the United States. C.D.C. officials were persuaded by new scientific evidence showing that even vaccinated people may become infected and may carry the virus in great amounts, Dr. Walensky acknowledged at the news briefing.

But she said masking is only a “temporary measure,” and, adding, “What we really need to do to drive down these transmissions in the areas of high transmission is to get more and more people vaccinated and in the meantime, to use masks.”

When asked whether he thought the C.D.C.’s new mask guideline could lead to some confusion, President Biden said on Tuesday afternoon that the pandemic was continuing “because of the unvaccinated, and they’re sowing enormous confusion.”

“The more we learn, the more we learn about this virus and the Delta variant the more we have to be worried and concerned,” he said. “There’s only one thing we know for sure, if those other hundred million people got vaccinated we’d be in a very different world. So get vaccinated, if you haven’t you’re not nearly as smart as I said you were.”

The C.D.C. should have simply made a universal recommendation and told all Americans to wear masks indoors, said Ali Mokdad, an epidemiologist at University of Washington and former C.D.C. scientist. “The director said the guidance is for people in areas of high transmission, but if you look at the country, every state is seeing a rise in transmission,” Dr. Mokdad said. “So why not say, ‘Everybody in the U.S. should be wearing a mask indoors?’ The whole country is on fire.”

Jesus Jiménez contributed reporting.