Nuon Chea, 92, was Pol Pot's deputy, and Khieu Samphan, 87, was the Cambodian regime's head of state.
They were on trial at the UN-backed tribunal on charges of genocide against Cham Muslims and ethnic Vietnamese.
The guilty verdict is the first official acknowledgement that what the regime did was in fact genocide as defined under international law.
The two men - already serving life sentences for crimes against humanity - have again been sentenced to life.
They are two of only three people ever convicted by the court in Phnom Penh.