"Brother Number Two" Nuon Chea, 87, and ex-head of state Khieu Samphan, 82, are accused of playing a leading role in the "Killing Fields" atrocities in the late 1970s that left up to two million people dead.
Prosecutor Chea Leang said life in prison was "the only punishment that they deserve".
"On behalf of the Cambodian people and the international community we ask you for justice -- justice for the victims who perished and justice for the victims who survived today who had to live through such a vicious and cruel regime under the leadership of these two accused and other leaders," she said.
The kingdom's UN-backed court is moving closer to a verdict in the complex trial of the two top leaders, which has been split into a series of smaller trials.
Life imprisonment is the maximum sentence it can deliver. There is no death penalty.
The first trial has focused on the forced evacuation of people into rural labour camps and the related charges of crimes against humanity.
The evacuation of Phnom Penh in April 1975 was one of the largest forced migrations in modern history.
The trial, which began hearing evidence in late 2011, is widely seen as a landmark in the nation's quest for justice.
Closing statements are scheduled to be completed by the end of the month, with a verdict expected in the first half of next year.
Other charges of genocide and war crimes are due to be heard in later hearings although no date has yet been set.
The defendants deny the accusations, saying they were not aware of the atrocities committed under the regime -- a claim rejected by prosecutors.
Another defendant, former foreign minister Ieng Sary died aged 87 in March this year, while the case against his wife Ieng Thirith -- also an ex-minister -- was suspended after the court ruled dementia left her unfit to stand trial.
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