"If you get vaccinated and your family's vaccinated, you can feel good about enjoying a typical Thanksgiving, Christmas with your family and close friends," Fauci, who is also director of the National Institute of Allergy and Infectious Diseases, said in an interview on Monday hosted by the Bipartisan Policy Center.
Fauci warned that cases are still high, so people should wear masks when they're out and about in the community and around groups of people in indoor settings.
"But when you're with your family at home, goodness, enjoy it with your parents, your children, your grandparents. There's no reason not to do that," Fauci said.
RELATED: CDC updates holiday guidance, urges vaccines and masking
Nearly 69% of people in the U.S. have gotten one dose of the vaccine. Recently, another 28 million children ages 5-11 also became eligible for vaccines.
But since late October, the U.S. has increased to 78,500 new cases a day, up by about 23% in the last two and a half weeks, data from the Centers for Disease Control and Prevention and Department of Human Health Services show. The increase has put a shroud of stress around holiday travel and planning.
"This will end, we are not going to be going through this indefinitely," Fauci said. "How quickly we get to the end depends on us, how well we vaccinate, how well we get boosted and how well we do the kinds of things to protect ourselves. So that's my message to the general public."
Twenty-one states -- many of them with colder temperatures -- have seen an uptick in daily cases of 10% or more in the last two weeks.
VIDEO: Simple tips to protect yourself from COVID this holiday season
Hospitalizations also grew last week -- the first national increase in total hospitalizations in nearly 10 weeks. There are more than 47,000 patients with COVID-19 currently receiving care, up by about 2,000 patients since last Monday.
For now, deaths are finally coming down from the 1,800 a day reported about two months ago, when cases and hospitalizations were spiking from the delta surge. The country is seeing about 1,000 new deaths a day. But the death toll is the most lagging statistic, often following rising cases and then increases in hospitalizations.
ABC News' Arielle Mitropoulos contributed to this report.