Fans from both sides flooded onto the field after the home team al-Masry scored a 3-1 win over Al Ahly, one of Egypt's biggest clubs.
Fans threw stones, fireworks and bottles. The dead and injured included security officers and some players.
State television gave no immediate cause for the deaths.
The country's deputy health minister Hesham Sheiha described the carnage as the "biggest disaster in Egypt's soccer history."
Al Ahli player Mohamed Abo Treika described the violence as war.
"This is not football," Treika said. "This is a war and people are dying in front of us.
"There is no movement and no security and no ambulances. I call for the premier league to be cancelled. This is horrible situation and today can never be forgotten."
The death toll figure came from the country's health ministry.
The head of Egypt's ruling military council, Mohamed Hussein Tantawi, said two helicopters were being sent to Port Said to fly out Al Ahli players and fans and transfer the injured to military hospitals.
Egypt's Muslim Brotherhood has accused supporters of ousted president Hosni Mubarak of instigating the violence.
"The events in Port Said are planned and are a message from the remnants of the former regime," Muslim Brotherhood spokesman Essam al-Erian said.
Another match in Cairo was halted by the referee after receiving news of the violence in Port Said, prompting fans to set parts of the stadium on fire, television footage showed.
All Egyptian league games have been suspended in the wake of the violence and Egypt's parliament was holding an emergency session.
FIFA boss Sepp Blatter described the riot as a "black day for football."
"I am very shocked and saddened to learn this evening that a large number of football supporters have died or been injured," Mr Blatter said in a statement.
"Such a catastrophic situation is unimaginable and should not happen. My thoughts are with the families of those who have lost their lives this evening."
Violence at football matches across north Africa has increased significantly since political unrest swept across the region in last year's Arab uprising.
ABC All Rights Reserved