The damning report, titled "Human Slaughterhouse: Mass hanging and extermination at Saydnaya prison" near Damascus, goes into excruciating detail about the gruesome ritual of mass hangings between 2011 and 2015.
At least once a week, up to 50 prisoners were taken out of their cells for arbitrary trials, beaten, then hanged "in the middle of the night and in total secrecy", the report said.
"Throughout this process, they remain blindfolded. They do not know when or how they will die until the noose was placed around their necks."
"They kept them (hanging) there for 10 to 15 minutes," a former judge who witnessed the executions said.
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"For the young ones, their weight wouldn't kill them. The officers' assistants would pull them down and break their necks."
Amnesty said the mass executions amounted to war crimes and crimes against humanity, but were likely still taking place.
Hamid, a former army officer who was jailed in 2012, told Amnesty he was simultaneously horrified and relieved when he saw prisoners being taken to be hanged.
In comments published Tuesday, Assad insisted that "defending" his country in a time of war was more important than a potential case against his government at the highest UN court in The Hague.
"We have to defend our country by every mean, and when we have to defend it by every mean, we don't care about this court, or any other international institution," he said.
Amnesty's report comes just two weeks before a new round of talks is due to take place in Switzerland aimed at putting an end to nearly six years of civil war.