Fully-vaccinated Americans are now allowed to travel without the need to quarantine, health officials have said.
People in the US who have had two doses of a coronavirus jab - or the single-shot Johnson & Johnson vaccine - can now travel at "low risk", the Centers for Disease Control and Prevention (CDC) said on Friday.
However, the CDC still discouraged Americans from doing so because of high coronavirus cases nationwide.
The new guidance means vaccinated citizens no longer need to quarantine or get tested if travelling within the US.
But if they are arriving from elsewhere, they need to show they have tested negative for COVID-19 before entering the country and get tested again three to five days after they land, according to the new CDC rules.
Addressing a White House briefing on jobs on Friday, President Joe Biden confirmed that more than 56 million of the US's population of 331 million have now been immunised.
But he warned that COVID cases are "going up again" and the virus is "spreading rapidly in many places".
The White House is not removing any of its guidance on face masks, with the Biden administration recommending people wear them in all public buildings and on transport.
Several states have decided to get rid of mandatory face masks in public places, however.
US officials have been under mounting pressure to change travel rules in recent weeks.
All of the major US airlines including American, Delta and United, called on the CDC to update its guidance so that "vaccinated individuals could travel safely".
US air travel is still 43% below pre-pandemic levels, according to the latest data.
But the administration fell short of removing restrictions on travel from China, Brazil, South Africa and large parts of Europe - in a bid to stop variants of the virus entering the country.
There are also still restrictions at the borders with Mexico and Canada.
Roger Dow, chief executive of the US Travel Association, said the "new travel guidance is a major step in the right direction that is supported by the science and will take the brakes off the industry that has been hardest hit by the fallout of COVID by far".
CDC director Rochelle Walensky added: "Vaccines can help us return to the things we love about life, so we encourage every American to get vaccinated as soon as they have the opportunity."
Mr Biden was speaking about the US March job report, which showed that 916,000 new jobs were added to the payroll nationwide last month.
It is the biggest recruitment increase since August, but the president still urged caution with the pandemic far from over.
"In the face of face of this great news, I need also to make this clear and direct statement to the American people: progress we've worked so hard to achieve can be reversed," he said.
