During the ceremony, known as the consistory, only 10 guests per cardinal were allowed in the St Peter’s Basilica due to the coronavirus pandemic. But despite the circumstances, the pope still gave each man their ring and traditional red hat, known as the biretta.
Two of the newly installed cardinals were not present at the ceremony, though, because they were unable to travel to Rome during the pandemic.
Mr Gregory, 72, was already the United States’ highest ranking African-American Catholic in the country’s history. He also was the only cardinal to represent the country during the ceremony on Saturday.
"It's been a time to thank God for this unique moment in my life and in the life of the church in the United States," Mr Gregory told CNN last week ahead of the ceremony. "I hope it's a sign to the African American community that the Catholic Church has a great reverence, respect and esteem for the people, for my people of color."
Each of the cardinals were required to quarantine for 10 days at the Vatican residences. Once they received three negative coronavirus test results, they were then allowed to participate in the ceremony on Saturday.
Everyone in the basilica wore a mask during the ceremony except the pope. The cardinals then each took off their mask, except for Mr Gregory who left his on, when they knelt before the pope to be invested.
Now as a cardinal, Mr Gregory will be one of Pope Francis’ closest advisers and one of just about 120 men who will select the next pontiff.
The Catholic Church now has 229 cardinals, 128 of whom are under 80 years old and eligible to vote for the next pope. Pope Francis has now named 73 of the 128 eligible to vote for the next pope.
“Among the people that have congratulated me and wished me well, friends and colleagues, I’ve heard this: It’s about time,” Mr Gregory said, referring to a Black American becoming a cardinal. “But it is also an important recognition that the African American, the Black Catholic community, is an important component within the larger, universal church.”
Mr Gregory made headlines in June after he blasted President Donald Trump for visiting St John’s Church near the White House for a photo opportunity.
In order to hold the event, which involved Mr Trump holding up a bible in front of the Catholic church, Washington DC police were ordered to disperse protesters outside the White House to allow for the president to make the walk.
Mr Gregory said he found it "baffling and reprehensible that any Catholic facility would allow itself to be so egregiously misused and manipulated".
Catholic conservatives condemned the statement made by the then-archbishop and instead sided with Mr Trump.
When speaking to Reuters on Tuesday, Mr Gregory said he hoped to find common ground with President-elect Joe Biden despite the pair disagreeing over abortions.
Additional reporting from Reuters