Survivors welcomed the remarks as a step towards achieving justice for the atrocities committed during the 1975-79 "Killing Fields" era.
"I am not trying to evade my responsibility," Nuon Chea, 86, who has denied charges of war crimes, genocide and crimes against humanity, said during his trial at a UN-backed court hailed as a key chance for reconciliation.
"As a leader, I must take responsibility for the damage, the danger to my nation," he said, expressing his "deepest condolences" to witnesses testifying at the tribunal who lost relatives under the regime.
At the same time Nuon Chea said that he was not aware of all of the Khmer Rouge's actions in his role overseeing propaganda and education.
"As for the executive branch, I had no power whatsoever. So about what happened during the Khmer Rouge period -- certain things I was aware of, but other things I was not aware of," he added.
Survivors welcomed the expression of remorse.
"This is the right thing to do. He accepts responsibility," said Bou Meng, 72, one of a handful of people to survive incarceration at the Khmer Rouge's Tuol Sleng prison in Phnom Penh.
Fellow survivor Chum Mey, 83, said Nuon Chea's remarks had reduced his own sense of anger towards the former Khmer Rouge number two.
"He accepted responsibility which is the right thing to do, and it's up to the court to judge his guilt," he said.
Nuon Chea, the most senior surviving leader of the "Killing Fields" era, is currently on trial alongside former Khmer Rouge head of state Khieu Samphan, 81, who has also denied charges of war crimes, genocide and crimes against humanity.
Khieu Samphan also expressed a "sincere apology" in court on Thursday and said that he was not aware at the time of the "great suffering" of the Cambodian people under the regime.
