The human rights group pointed the finger of blame mostly at U.S. forces, saying that of the 140 civilian deaths it investigated between 2009 and 2013, none were prosecuted by the American military.
Amnesty said it is only aware of six cases having been investigated since 2009.
In the report released Monday, Amnesty did note that the majority of innocent casualties in more than 12 years of warfare have been caused by the Taliban and other insurgent groups.
But Richard Bennett, the group's Asia-Pacific director, said there is evidence that suggests some of the killings attributed to NATO forces were deliberate and in possible violation of international law.
"Evidence of possible war crimes and unlawful killings has seemingly been ignored," Bennett said in a statement.
At least 50 children were reportedly among the dead in the 10 separate incidents that Amnesty examined.
The group said it interviewed 125 witnesses, victims and family members, including many who had never given testimony to anyone before.
When civilian casualties are reported and NATO announces an investigation, Bennett says Afghan witnesses are rarely interviewed or even contacted.
"The victims and their families have little chance of redress," he said. "The U.S. military justice system almost always fails to hold its soldiers accountable for unlawful killings and other abuses."
The report singles out U.S. special forces in two cases, one of which the human rights group said involved the torture of a man detained during a raid on Nerkh in Wardak province, a notoriously dangerous area southwest of Kabul.
The prisoner quoted in the report, Qandi Agha, even claimed to have witnessed the killing of another detainee.
The report makes no mention of Canadian troops, who fought a five-year guerilla war in Kandahar, but does say Canada's military justice system has more civilian oversight and control, which puts it in a better position than the U.S.
"There is an urgent need to reform the U.S. military justice system," said Bennett. "The U.S. should learn from other countries, many of which have made huge strides in recent years in 'civilianizing' their military justice systems."
Not long after arriving in Kandahar in 2006, Canadian troops were involved in a series of shooting incidents in which civilians died. The mounting death toll into 2007 forced commanders on the ground to put tougher rules in place.
Both the United Nations and Amnesty International criticized Canada in 2008 over civilian casualties.
Philip Alston, the United Nation's special rapporteur on extrajudicial, summary or arbitrary executions, was particularly strong in his criticism in the deaths of two men, Abdul Habib and Mohammed Ali, who were killed in their home by "international forces."
The general in charge of Canada's overseas and domestic command said he had not seen the latest Amnesty report and did not want to comment on its contents.
But, Lt.-Gen. Stuart Beare, who served as deputy head of the NATO training mission in Afghanistan, said Canada learned from its mistakes.
"There was adaptation and self-correction," he said in an interview with The Canadian Press. "These were new experiences for us too."
The Canadian military justice system is "a vital component of who we are and what we do, and it works for us in a very unique Canadian way," Beare added.
Though not an example that involved the death of a civilian, several officials at National Defence pointed Monday to the case of Capt. Robert Semrau as an example of how the system worked.
Semrau was court-martialled in 2010 for the battlefield execution of a wounded Taliban fighter in Afghanistan two years earlier. He was acquitted of second-degree murder, attempted murder and the negligent performance of a military duty, but found guilty of disgraceful conduct.