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The Centers for Disease Control and Prevention also said people no longer need to stay at least 6ft (about 2 metres) away from others.
The changes are driven by a recognition that more than two and a half years since the start of the pandemic an estimated 95% of Americans ages 16 and older have acquired some level of immunity, either from being vaccinated or infected, agency officials said.
The CDC recommendations apply to everyone in the US, but the changes could be particularly important for schools, which resume classes this month in many parts of the country.
Perhaps the biggest education-related change is the end of the recommendation that schools do routine daily testing, although that practice can be reinstated in certain situations during a surge in infections, officials said.
Masks continue to be recommended only in areas where community transmission is deemed high, or if a person is considered at high risk of severe illness.
School districts across the US have been scaling back their Covid-19 precautions in recent weeks even before the CDC relaxed its guidance.
Some have also been moving away from test-to-stay programs that became unmanageable during surges of the Omicron variant last school year. With so many new infections among students and staff, many schools struggled to track and test their close contacts, leading to a temporary return to remote classes in some places.
The average numbers of reported Covid-19 cases and deaths have been relatively flat this summer, at about 100,000 cases a day and 300 to 400 deaths.
The CDC previously said that if people who are not up to date on their Covid-19 vaccinations come into close contact with a person who tests positive, they should stay home for at least five days. Now the agency says quarantining at home is not necessary, but it urges those people to wear a high-quality mask for 10 days and get tested after five.
The agency continues to say that people who test positive should isolate from others for at least five days, regardless of whether they were vaccinated. CDC officials advise that people can end isolation if they are fever-free for 24 hours without the use of medication and they are without symptoms or the symptoms are improving.
