The warrant was ordered by a Swiss court last year but made public only on Wednesday, according to activists who filed a criminal complaint.
It calls for Rifaat Al Assad to be extradited from Syria, where he returned from exile in 2021 after having assets frozen in France.
The Justice Ministry had initially denied the prosecutors' bid to arrest Mr Al Assad, 85, arguing Switzerland did not have jurisdiction to pursue him.
It was argued he was neither a Swiss citizen, nor residing in the country, and that no Swiss citizens were among the victims of the 1982 massacre in the Syrian city of Hama at the centre of the case.
But the court did not share that interpretation, saying he was staying at a Geneva hotel when Swiss prosecutors first launched their investigation into him in 2013.
That presence was enough, according to the court, to give Switzerland jurisdiction to pursue him over alleged war crimes, including the issuance of an international arrest warrant.
The warrant is meanwhile likely to go unheeded. The younger brother of former Syrian president Hafez Al Assad returned to the country in 2021 after 37 years in exile.
Separately implicated in French and Spanish corruption cases, he was forced into exile in 1984 after a failed attempt to overthrow his brother.
France's highest court last year confirmed a ruling that found him guilty of acquiring millions of euros' worth of property using funds diverted from the Syrian state.
The war crimes complaint was first filed a decade ago by Trial International, a human rights group that works with victims and pushes Switzerland to prosecute.
It said much of the evidence it had compiled against Mr Al Assad relates to his role in suppressing the 1982 Hama rebellion, where thousands of people were estimated to have been killed and two thirds of the city destroyed.
He was at the time in command of the Syrian Defence Forces, which is accused of "executions, enforced disappearances, rape and torture on an unimaginable scale", according to Trial. It cited estimates that as many as 40,000 people were killed across a three-week span.
In a statement, the organisation on Wednesday called on Swiss authorities to "swiftly indict and bring to trial the man nicknamed the 'Butcher of Hama'".
"It is to be welcomed that the prosecuting authorities have finally decided to request Mr Al Assad's extradition, although it is regrettable that we had to wait until his return to Syria before demanding he appear before the Swiss courts," Benoit Meystre, a legal adviser, said in the statement.