Police moved in and fired tear gas to break up the crowds at around 2 a.m., and protesters responded with volleys of stones in battles near a memorial to former President Anwar Sadat, who was assassinated in 1981.
Gunshots also rang out, seemingly from both sides, said one witness, Mosa'ab Elshamy, a freelance photographer, though he could not tell who started firing.
Armed residents of the area also joined the police side, and there were also plainclothes police carrying handguns, he said.
"They aimed at killing the people. They aimed the head and the neck," said Ahmed Abdullah, a doctor at a field clinic set up at Rabaah al-Adawiya, as he wiped away tears.
At the Rabaah al-Adawiya clinic, men shouted "God is great," and women wailed as bodies were loaded into ambulances to be taken for examination at hospitals. Bodies of more than a dozen men lay on the blood-splattered floor with white sheets over them.
Ragab Nayel Ali, one of the pro-Morsi protesters, said security forces fired first with tear gas and birdshot. "Protesters replied by hurling rocks and started building walls," said Ali, who was injured in an accident as he ferried wounded on his motorcycle from the fighting to a field hospital.
Health Ministry spokesman Khaled el-Khateeb said that at least 65 people were killed and 270 wounded. Nine more were killed in clashes in the Mediterranean city of Alexandria since Friday, he said.
A Brotherhood spokesman, Ahmed Aref, told reporters that 66 were killed in the Cairo violence and another 61 were "clinically dead." He did not further explain their condition.
The Interior Ministry said 14 policemen were wounded, two with gunshot wounds to the head.
Clashes in Alexandria erupted on Friday and extended into the night as more than 100 Morsi supporters took refuge in a central mosque, holding captive 17 of their rivals as they tried to fend off a security siege of the building. A security official said the hostages were freed and those inside the mosque arrested. The official spoke on condition of anonymity because he was not authorized to speak to the media.