Clooney, a British-Lebanese lawyer human rights lawyer and activist, also accused the United Nations of "inaction" towards the extremist groups' ongoing crimes against humanity, expressing her frustration at the fact that no serious action had been taken against the group in the six months since she had last addressed the UN.
"Excellencies, ladies and gentlemen, what is shocking here is not just the brutality of ISIS but how long those who know about it can remain passive. If we do not change course, history will judge us, and there will be no excuse for our failure to act," Clooney said.
"Justice is what the victims want, but justice will be forever out of reach if we allow the evidence to disappear, if mass graves are not protected, if medical evidence is lost, if witnesses can no longer be traced," she stressed.
Nadia Murad, a Yazidi victim of ISIS (Daech) who has spoken out against the group since her release from captivity in 2014, also spoke out.
She urged the UN not to let ISIS get away with the atrocities they have committed.
"Why it is taking so long?" Murad asked. "I cannot understand why you are letting ISIS get away with it, or what more you need to hear before you will act,” she continued.
Murad who has been appointed as a goodwill ambassador for the Dignity of Survivors of Human Trafficking for UNODC, is represented by Clooney.
And they both have been vocal about the urgent need for legal action to be taken against the crimes committed by ISIS.
The UN had previously released reports recognizing the crimes committed against the Yazidi community by ISIS in Iraq as a genocide.
A plea to Iraq's Prime Minister
Clooney asked for witness evidence to be recorded, regardless of whether the move is approved by Iraqi Prime Minister, Haidar al-Abadi, who was in attendance.
She also urged him to send a letter to the UN Security Council so it can vote to set up an investigation into crimes by the group in Iraq, according to The Independent.
Clooney ended her speech with a passionate call for action.
"Don't let this be another Rwanda, where you regret doing too little, too late. Don't let Isis get away with genocide," she said.