The historic international court issued its ruling on an appeal by Khieu Samphan, who served as head of state in Cambodia's 1975-79 Khmer Rouge government.
He was convicted in 2018 of genocide, crimes against humanity and war crimes and sentenced to life in prison.
The tribunal spent $US337 million ($A506 million) and 16 years to convict just him and two other defendants in connection with a reign of terror that caused the deaths of an estimated 1.7 million people.
Australia has been a key supporter of the tribunal, providing substantial funding for it along with the US and Japan.
Samphan appeared in court in a white windbreaker, wearing a face mask and listening to the proceedings on a pair of headphones. Seven judges were in attendance.
He was the group's nominal head of state but, in his trial defence, denied having real decision-making powers when the Khmer Rouge carried out a reign of terror to establish a utopian agrarian society, causing Cambodians' deaths from execution, starvation and inadequate medical care.
It was ousted from power in 1979 by an invasion from neighbouring communist state Vietnam.
Samphan alleged in his appeal the court made errors in legal procedures and interpretation and acted unfairly.
But the court noted on Thursday that his appeal did not directly question the facts of the case as presented in court. It ruled point by point on the arguments raised by Samphan, rejecting virtually all and saying its final judgment of several hundred page would be official when it is published.
The final ruling makes little practical difference. Samphan is 91 and already serving another life sentence for his 2014 conviction for crimes against humanity connected with forced transfers and disappearances of masses of people.
His co-defendant Nuon Chea, the Khmer Rouge's number two leader and chief ideologist, was convicted twice and received the same life sentence. He died in 2019 at age 93.
The tribunal's only other conviction was that of Kaing Guek Eav, also known as Duch, who was commandant of Tuol Sleng prison, where roughly 16,000 people were tortured before being taken away to be killed. Duch was convicted in 2010 of crimes against humanity, murder, and torture and died in 2020 at age 77 while serving a life sentence.
The Khmer Rouge's real chief, Pol Pot, escaped justice. He died in the jungle in 1998 at age 72 while the remnants of his movement were fighting their last battles in the guerrilla war they launched after losing power.
The trials of the only other two defendants were not completed. The former foreign minister of the Khmer Rouge, Ieng Sary, died in 2013, and his wife, former Social Affairs Minister Ieng Thirith, was deemed unfit to stand trial due to dementia in 2011 and died in 2015.
Four other suspects, middle-ranking Khmer Rouge leaders, escaped prosecution because of a split among the tribunal's jurists.
In an innovative hybrid arrangement, Cambodian and international jurists were paired at every stage, and a majority had to assent for a case to go forward.
Under the French-style judicial procedures the court used, the international investigators recommended the four go to trial but the local partners would not agree after Cambodian Prime Minister Hun Sen declared there would be no more prosecutions, claiming they could cause unrest.
Hun Sen himself was a middle-ranking commander with the Khmer Rouge before defecting while the group was still in power, and several senior members of his ruling Cambodian People's Party share similar backgrounds. He helped cement his political control by making alliances with other former Khmer Rouge commanders.
With its active work done, the tribunal, formally called the Extraordinary Chambers in the Courts of Cambodia, now enters a three-year "residual" period, focusing on getting its archives in order and disseminating information about its work for educational purposes.
