The sentences at the Fourth Criminal Court in Damascus are the first against Assad or members of his inner circle since the Assad family's five decades in power came to an end 20 months ago.
"Bashar Assad used state agencies to commit war crimes and crimes against humanity," said judge Fakhareddine al-Aryan during a court session that was aired live on state TV on Tuesday.
Also sentenced to death was Assad's maternal cousin Atef Najib, who was convicted of overseeing a crackdown in the southern province of Daraa that led to the uprising and later the civil war.
Al-Aryan said Najib can appeal.
Under tight security, Najib stood inside a cage wearing a prisoner's uniform as the judge read the sentence.
A crowd gathered outside the courthouse in central Damascus to hear the verdict.
"Today is the day of justice for all the wounded, martyrs, detainees and Syrians who were forced to leave their country," said lawyer Adnan al-Masalmeh, who represented families of Najib's victims.
"Today marks a victory of right against injustice, a victory of the Syrian people against the ousted regime."
Assad and his brother Maher fled to Russia after the government's fall in December 2024 and received political asylum.
Syria's new rulers have asked Russia to hand the Assads over.
Najib, who was sanctioned by the US Department of the Treasury in April 2011, was later detained and is one of the highest-ranking security officials to be put on trial.
Najib is a former army brigadier general who was head of the Political Security Branch in Syria's southern Daraa province under Assad in 2011.
During his tenure, more than a dozen teenagers who scrawled anti-government graffiti on a school wall in Daraa were arrested and tortured.
The case became a catalyst for mass protests against the repressive policies of Assad's security forces.
The protests were met by a brutal government crackdown that spiralled into a 14-year civil war that ended with Assad's ouster in a lightning rebel offensive.
Maher Assad was a former commander of the Syrian military's 4th Armored Division - which opposition activists have accused of killings, torture, extortion and drug trafficking, as well as running its own detention centres.
"Today's scenes outside the courthouse reflect 15 years of pain and a justice long denied. Human Rights Watch opposes the death penalty in all cases, including this one," said Hiba Zayadin, Syria researcher at Human Rights Watch.
"It's cruel and irreversible, especially when a fair trial isn't guaranteed."
Zayadin said Najib had the right to appeal, and that process "needs to meet fair trial standards too".
Real accountability for Assad-era crimes depended on Syria building a justice system that lasted, she said.
