The human rights group's report follows acknowledgement from the coalition that the US military was behind a March 17 strike in a western Mosul neighborhood that residents have said killed more than a hundred civilians.
US officials did not confirm there were civilian casualties but opened an investigation.
Amnesty's report also cites a second strike on Saturday that it said killed "up to 150 people." The US-led coalition said in a statement that it was investigating multiple strikes in western Mosul that resulted in civilian deaths.
Evidence gathered on the ground in Mosul "points to an alarming pattern of US-led coalition airstrikes which have destroyed whole houses with entire families inside," the report stated, according to AP.
It said any failure to take precautions to prevent civilian casualties would be "in flagrant violation of international humanitarian law."
In Baghdad, visiting US army chief of staff, Gen. Mark A. Milley, said on Monday that what caused the explosion was still unkown and added that "some degree of certainty will be known in the coming days following the investigation."