The New York-based rights group called on the U.N. Security Council to refer the situation in Syria to the International Criminal Court.
The security sweep in Talkalakh, which lasted less than a week, contributed to a growing sense of desperation over the government's brutal crackdown on protests as the nationwide uprising against President Bashar Assad's authoritarian regime gained traction.
At the time of the operation, The Associated Press interviewed residents who told of a catastrophic scene in the town of about 70,000, including sectarian killings, gunmen carrying out execution-style slayings and the stench of decomposing bodies in the streets.
Some activists have said the death toll from the May siege was as high as 36 people.
"The accounts we have heard from witnesses to events in (Talkalakh) paint a deeply disturbing picture of systematic, targeted abuses to crush dissent," said Philip Luther, Amnesty International's Middle East and North Africa Deputy Director.
The report issued Wednesday said the attacks "appear to be part of a widespread, as well as systematic, attack against the civilian population," which would constitute crimes against humanity.
Talkalakh is just across the border from Lebanon.
Amnesty quoted witnesses as saying Syrian forces fired on fleeing families and ambulances carrying the wounded; one witness said soldiers stabbed lit cigarettes on the backs of detainees' necks.
At least nine people died in custody, witnesses told Amnesty. Eight of them were shot at and wounded as they were ordered out of a house, and were then taken away by soldiers.
Amnesty cited interviews carried out in Lebanon and by phone with more than 50 people. The rights group, along with most foreign media, has not been allowed to enter Syria.
The 14-week uprising against Assad has proved resilient despite a deadly government crackdown that has brought international condemnation and sanctions. Assad is facing the most serious challenge to his family's four decades of rule in Syria.
Activists say security forces have killed more than 1,400 people — most of them unarmed protesters — since mid-March. The regime disputes the toll, blaming "armed thugs" and foreign conspirators for the unrest.
According to Amnesty, some of the family members who went to identify the bodies of their sons in Talkalakh were forced to sign a document stating that their sons were killed by armed gangs.
"Most of the crimes described in this report would fall within the jurisdiction of the International Criminal Court," Luther said. "But the UN Security Council must first refer the situation in Syria to the Court's Prosecutor."
Four European countries have introduced a draft resolution in the Security Council that would condemn Syria's crackdown on protesters, but Russia and China have indicated they would veto it.