Demonstrators complained about a lack of freedom and the worsening economic situation during the rare protests, according to people who spoke to CNN and videos from multiple cities, including capital Havana.
Many chanted for "freedom" and called for President Miguel Díaz-Canel to step down, Reuters reported.
Multiple protesters were arrested by police, who used tear gas to break up some demonstrations.
In a nationally televised address, President Díaz-Canel said US trade sanctions had created economic misery on the communist-run island. Díaz-Canel did not offer the protesters any concessions in his speech.
"The order to combat has been given," he said at the end of his appearance, "Revolutionaries need to be on the streets."
In the city of San Antonio de los Baños, just outside Havana province, hundreds of people defied a heavy police presence to air their complaints.
One resident who did not wish to be identified told CNN that residents had been enduring power outages for a week and that had "detonated" the growing outrage.
Videos uploaded to social media appeared to show other protests in a handful of cities and towns across the island.
In some of the videos, people shouted they "weren't afraid" or that they wanted liberty or access to coronavirus vaccines.
White House National Security Advisor Jake Sullivan tweeted support for the Cuban people Sunday night saying, "the U.S. supports freedom of expression and assembly across Cuba, and would strongly condemn any violence or targeting of peaceful protesters who are exercising their universal rights."
The U.S. supports freedom of expression and assembly across Cuba, and would strongly condemn any violence or targeting of peaceful protesters who are exercising their universal rights. https://t.co/FjI8bUHoQE— Jake Sullivan (@JakeSullivan46) July 12, 2021
Other US officials also urged for restraint, saying Cubans had the right to protest.
"We are deeply concerned by "calls to combat" in #Cuba. We stand by the Cuban people's right for peaceful assembly. We call for calm and condemn any violence," Julie Chung, acting assistant secretary for the Department of State's Bureau of Western Hemisphere Affairs, tweeted Sunday.
"For decades, Cuba's dictatorship has used violence and repression to silence its people, rather than permit the free exercise of democracy and their basic social rights," Senate Foreign Relations Committee Chairman Bob Menendez said in a statement.
Tonight we bear witness as Cubans take to the streets despite ongoing persecution to call for the dictatorship's end. We must stand in solidarity as they ask nothing more than to be able to speak their minds freely, openly & without fear. FULL STATEMENT: https://t.co/dIGEAzYZ9d— Senate Foreign Relations Committee (@SFRCdems) July 12, 2021
"This must end. The world's eyes are on Cuba tonight and the dictatorship must understand we will not tolerate the use of brute force to silence the aspirations of the Cuban people," he added.
US-Cuban relations are at their lowest point in years. The Trump administration enacted some of the toughest economic measures against Cuba in decades, and so far, the Biden administration seems reluctant to lift them.
The already struggling Cuban economy has been hit hard as tourism and good imports have dropped steeply during the pandemic.
On Sunday, Cuban health officials reported a record single-day increase for new Covid-19 cases and deaths.
The-CNN-Wire & 2021 Cable News Network, Inc., a WarnerMedia Company. All rights reserved.