Biden, speaking to reporters at a White House meeting Monday, addressed what he called "the remarkable protests" in Cuba of people "demanding their freedom from an authoritarian regime."
"And I don't think we've seen anything like this protest in a long, long time -- if, quite frankly, ever. And the United States stands firmly with the people of Cuba as they assert their universal rights, and we call on the government, the government of Cuba, to refrain from violence and their attempts to silence the voice of the people of Cuba," he said.
Cuba's communist leadership has already denounced the protests as a "systemic provocation" by Cuban dissidents and the U.S. government, encouraged its supporters to counter-protest, and sent its armed forces into the streets, risking clashes with demonstrators.
In a statement earlier Monday, Biden said, "We stand with the Cuban people and their clarion call for freedom and relief from the tragic grip of the pandemic and from the decades of repression and economic suffering to which they have been subjected by Cuba's authoritarian regime."
"The Cuban people are bravely asserting fundamental and universal rights. Those rights, including the right of peaceful protest and the right to freely determine their own future, must be respected. The United States calls on the Cuban regime to hear their people and serve their needs at this vital moment rather than enriching themselves," he said.
Sunday's protests, in several cities across the island, are some of the biggest anti-government demonstrations in Cuba's recent history, and Biden had been called on to show support for the protests.
While he helped the Obama administration's efforts to ease tensions with Cuba and reopen trade and travel, Biden has kept most of former President Donald Trump's sanctions and restrictions in place on America's close neighbor and longtime adversary.
The administration says it is still reviewing its Cuba policy, earning the ire of progressives in the Democratic Party, but with these nearly unprecedented demonstrations, it may have to move more quickly than it hoped.
So far, the administration has voiced support for the Cuban people's right to peacefully assemble and condemned any violence. Prior to Biden's statement, acting Assistant Secretary of State for the Western Hemisphere Julie Chung and Biden's national security adviser Jake Sullivan weighed in with that sentiment.
Cuban President Miguel Díaz-Canel acknowledged public grievances over blackouts and food and medicine shortages during a televised address Monday, but he blamed the island nation's problems on the long-standing U.S. embargo and accused American "imperialists" of stoking tensions on social media.
"Yesterday, Cuba lived the most heroic day. Thousands of patriotic people defend the Revolution," he said on state television, referring to pro-government demonstrations in Havana later on Sunday that numbered around 300, according to the Associated Press.
"We do not want to hurt our beloved people," added Díaz-Canel, who assumed the presidency in 2019 and became the first secretary of the Cuban Communist Party this April, officially taking over for Raúl Castro.
Cuba's Minister of Foreign Affairs Bruno Rodríguez Parrilla had even sharper words Monday, firing back at Sullivan and Chung's statements of support for protests by saying the White House has "no political or moral authority to speak about Cuba."
"His government has allocated hundreds of millions of dollars to promote subversion in our country & implements a genocidal blockade, which is the main cause of economic scarcities," he tweeted, referring directly to Sullivan's statement.
Cuba is going through its worst economic crisis in decades, with its economy contracting by double-digits last year. But along with the economic crisis, the country is dealing with another deadly surge of COVID-19.
ABC News' Christine Theodorou and Molly Nagle contributed to this report.