The court upheld the death sentence for 21 defendants in the case, and sentenced two ex-senior police officers to 15 years in prison while acquitting seven others, China's official Xinhua news agency reported.
Judge Sobhi Abdel-Maguid confirmed the capital punishment sentences and specified "death by hanging," the BBC reported.
The defendants were accused of being involved in the killing 72 people during a riot following a soccer game in Port Said in February 2012.
Violent protests broke out after the court's ruling. Families of those sentenced to death said the penalties are too harsh, while members of Ultras Ahlawy, a soccer fan group based in Cairo, said the penalties for the police officers were too lenient.
Ahram Online reported Ultras Ahlawy protesters began to gather outside the courthouse while awaiting the verdict in the case.
"One [protester] was shot dead while the other died of suffocation due to inhaling tear gas," Mohamed Sultan, Head of Egypt's Ambulance Authority told Xinhua.
Egyptian Interior Minister Mohamed Ibrahim fired key security chief Maged Nouh following widespread sit-ins staged by security force personnel.
Ibrahim replaced Nouh with Ashraf Abdallah, a veteran Central Security Forces officer Friday, al-Masry al-Youm reported. Abdallah's first challenge will be to negotiate an end to the officers' strike, the newspaper said.
The Interior Ministry said the army would take over the headquarters of the Port Said Security Directorate.
Violent protests in Port Said this week have left at least seven people dead and dozens injured, Ahram Online reported.
In a statement on its Facebook page, the ministry urged the people of Port Said to "calm the situation and ensure the safety of all government and private establishments," al-Masry al-Youm said.