The process concerns the shooting down, 30 years ago, of two aircraft belonging to a Cuban exile group.
Castro, who was defense minister at the time of the incident, is accused of murder, among other things.
"We expect that he will show up here of his own accord, or by other means, and be put in prison," said US Acting Attorney General Todd Blanche at a press conference in Miami.
The announcement comes at a time when the United States has put heavy pressure on Havana - and is raising new speculation about whether Washington is planning to overthrow Cuba's communist regime.
"Falling apart"
When the United States attacked Venezuela in January and kidnapped President Nicolás Maduro, Donald Trump used a legal process to justify the attack.
"This is a big moment," Trump told reporters when asked about the indictment on Wednesday.
Trump added that "there will be no escalation."
"I don't think it's necessary. Cuba is falling apart. It's a mess; they've kind of lost control."
Energy crisis
Following the attack on Venezuela, Washington has cut off fuel supplies to Cuba, leading to acute energy shortages and a deepening economic crisis. Trump has also threatened on several occasions to take control of the island.
The indictment against Castro is a "political maneuver completely without legal basis" aimed at "justifying the madness of a military aggression against Cuba," writes Cuban President Miguel Díaz-Canel on X.
Earlier on Wednesday, US Secretary of State Marco Rubio urged the Cuban people to demand a new government.
"We are ready to begin a new chapter in the relationship between our peoples," Rubio said in a video statement in Spanish.
Raúl Castro formally stepped down as leader of Cuba's Communist Party in 2021, but is still seen as one of the country's most powerful figures. He is the brother of revolutionary leader and former president Fidel Castro.
