In Florida, state police dispersed an unauthorised gathering of hundreds of people in Daytona Beach on Saturday.
In Missouri, bars at the Lake of the Ozarks were packed with revellers, who violated social-distancing rules.
US coronavirus task force chief Dr Deborah Birx said she was "very concerned" after seeing such scenes.
"We really want to be clear all the time that social distancing is absolutely critical. And if you can't social distance and you're outside, you must wear a mask," Dr Birx said on ABC's This Week on Sunday.
Lyda Krewson, the mayor of St Louis, Missouri, said: "It's irresponsible and dangerous to engage in such high risk behaviour just to have some fun over the extended holiday weekend.
"Now, these folks will be going home to S. Louis and counties across Missouri and the Midwest, raising concerns about the potential of more positive cases, hospitalisations, and tragically, deaths. Deeply disturbing."
In Florida's Tampa area, the crowds were so big that authorities closed parking lots because they were full, the Associated Press reports.
In California, big crowds were seen enjoying beaches over the weekend. State officials said most people were covering their faces and keeping their distance on beaches and parks.
On Monday, US Vice-President Mike Pence said that some people "would do well to be reminded about the importance of social distancing and the importance of continuing regular hygiene".
However, he added: "We have every confidence that as restrictions are loosened in the days ahead, the American people are going to step forward and put this country back to work in a safe and responsible way."
Memorial Day - an annual holiday held on the last Monday of May - honours all those who have died serving in the US military. It marks the unofficial start of summer.
The US has more coronavirus cases than anywhere in the world. It has over 1.6 million known infections and is nearing 100,000 deaths linked to the virus.
All 50 US states have now partially reopened after a two-month shutdown. However, remaining restrictions vary across the country.
Wide discrepancies also remain between states in terms of infection rates and the pace of their economic restart.
Some of the hardest-hit areas, including New York, New Jersey and Washington state are now showing the sharpest declines, while majority of states have reached plateaus.