Wednesday's total eclipses the previous high of new cases reached on June 26, when 45,255 new coronavirus cases were reported across the US.
It took a little more than two months for the US to record its first 48,000 cases, the university's data says.
There have been 2,683,894 cases of coronavirus in the country, according to Johns Hopkins University. More than 128,000 people have died.
At least five states -- Arizona, California, North Carolina, Tennessee, Texas -- had record-high totals of new case reports on Wednesday.
California, the most populous state, reported 9,740 new cases. That figure included 5,898 cases reported to the state in the past 24 hours and 3,842 previously unreported cases from a five-day period, Ali Bay, a spokeswoman for the state's joint information center, said.
The spike comes as many states are pausing their reopenings or rolling back some restrictions.
More than 28 million Californians live in counties where restaurant dining rooms, bars and other indoor facilities are being told to stay shut or close as the number of Covid-19 cases continue to worry state officials.
The closures affect 19 counties representing 72% of the state's population, and include restaurants, museums, zoos, movie theaters, family entertainment, and card rooms, Gov. Gavin Newsom said Wednesday.
The governor's announcement included bars, pubs, breweries and wineries that don't also serve food. Restaurants can serve takeout meals.
"Bottom line is, the spread of this virus continues at a rate that is particularly concerning," said Newsom, who added that the percentage of people who test positive is rising.
These restrictions will remain in place for at least three weeks, Newsom said.
Newsom said California's state beaches in areas where local governments have closed theirs will also be closed. Parking lots at state beaches that are open in Southern California and the Bay Area won't be operating.
California isn't the only state that announced new restrictions. Michigan is closing indoor service at bars throughout most of the lower part of the state. Governors in Pennsylvania and Oregon ordered their citizens to wear face coverings.
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Weekend could be a 'perfect storm'
As the Fourth of July weekend nears, an infectious disease doctor said the United States could be heading into "the perfect storm" for a spike in coronavirus cases.
"It's set up a perfect storm: the combination of travel, the combination of reopening -- perhaps in some cases, too early -- and the combination of people not necessarily following some of these preventive guidelines," Dr. Joshua Barocas, an infectious disease physician at Boston Medical Center, said during a Wednesday briefing by the Infectious Diseases Society of America.
Barocas said cases spiked in some states after Memorial Day. Thirty-seven states now trend upward in the number of cases from last week and only two states, New Jersey and Rhode Island, trend downward.
