Some traditions have continued, like the annual Macy's Thanksgiving Day Parade in New York City, which was closed to spectators.
Many have also travelled home to celebrate the holiday, despite warnings from health officials.
More than three million people are reported to have travelled through US airports from Friday to Sunday in what was the busiest travel weekend since the outbreak began in mid-March.
But the number is around half the usual figure for Thanksgiving travel, and many people have opted out of seeing friends and family for the holiday.
Many still managed to mark the occasion in different ways.
For those living in sunnier climes, it was a bit easier to socialise outdoors.
Thanksgiving, which sees Americans gather with their families for festivities on a scale rivalling Christmas, falls on the fourth Thursday of November. This year is the holiday's 400th anniversary.