Friday's sentencing is the first time the charge of genocide was ever levied against any senior leader of the ultra-Maoist regime, which left an estimated two million Cambodians dead during its four-year reign of terror.
Here is a look back at some key moments in the historic trial.
- Referred to court -
After years of preparation and investigation, on January 13, 2011 four senior leaders are referred to the war crimes tribunal set up on the outskirts of Phnom Penh, formally called the Extraordinary Chambers in the Courts of Cambodia (ECCC).
They are "Brother Number Two" Nuon Chea, rumoured to be the second-in-command to Khmer Rouge leader Pol Pot; head of state Khieu Samphan; foreign minister Ieng Sary; and his wife, Ieng Thirith, who was the social affairs minister during the regime.
She is released the following year, suffering from dementia, while Ieng Sary dies in detention in 2013 at the age of 87.
The trial begins on June 27, 2011 but facing criticism that it would take too long, the judges decide three months later to split the proceedings into two: a first "mini-trial" which will focus on "crimes against humanity"; and the second on charges of "genocide".
- 'Not bad people' -
The end of 2011 is marked by memorable testimony by the two defendants.
Khieu Samphan in November hits back at the prosecution for telling "fairy tales" about the Khmer Rouge, insisting that most Cambodians supported the brutal regime.
A month later, Nuon Chea -- regarded as the chief ideologue for the movement -- says the Khmer Rouge were not "bad people" or criminals.
"I don't want the next generations to misunderstand history," he tells the court on December 5, 2011. "Nothing is true about that."
- Life imprisonment -
Nuon Chea on May 30, 2013 shows the first signs of remorse when he admits he must "take responsibility for the damage" done to Cambodia and expresses his "deepest condolences".
Yet the truculent defendant stops short of admitting guilt to the charges of genocide, war crimes and crimes against humanity, denying any knowledge when it came to the regime's worst atrocities.
Earlier that month Khieu Samphan offered a "sincere apology" but attempted to distance himself from the regime's actions, saying he was unaware of his fellow Cambodians' suffering.
The following year on August 8, 2014, the two are found "guilty of crimes against humanity or extermination ... political persecution and other inhumane acts" and jailed for life -- a sentence that causes survivors to burst into applause as they weep after a 35-year wait for justice.
- Genocide -
The second "mini-trial" begins July 30, 2014, examining the charges of genocide of ethnic Vietnamese and Muslim Cham minorities. Controversially, these charges do not cover the mass killings of Khmers by Khmers, as the United Nations does not consider that to be genocide.
In September 2016, witnesses testify to how Cham Muslims were mistreated, forced to eat pork and banned from speaking their language while copies of the Koran were burned by Khmer Rouge cadres.
It is estimated that 100,000 to 500,000 Cham Muslims and 20,000 Vietnamese were murdered under the regime.
After almost 300 days of trial of this second "mini" case, June 23, 2017 is the last day of hearing. Over three years, more than 100 witnesses took the stand to denounce the regime's practice of forced marriages, rape, and mass killings.
On November 16, 2018, the two are sentenced to life in prison on charges of genocide.
The tribunal issues a landmark verdict stating that Nuon Chea is guilty for all crimes perpetrated during the Khmer Rouge regime, given his senior role as second-in-command to Pol Pot.
Khieu Samphan is found guilty of genocide against the ethnic Vietnamese, but not of Cham Muslims.