The flames blocked the entrance to the church and many of the dead, including several children, were trampled to death as panic broke out, Reuters reports.
15 fire engines were dispatched to the scene to extinguish the flames while ambulances took the injured to nearby hospitals.
Early information indicates that the fire is due to an electrical fault. Fire accidents are not uncommon in Cairo, where millions of Egyptians live in simple conditions.
The church is located in the densely populated district of Imbaba, and an estimated 5,000 people are said to have flocked there to attend a mass.
President Abd al-Fattah al-Sisi has spoken by phone with Coptic Christian Pope Tawadros II to express his condolences, the president’s office said.
Copts make up about ten percent of Egypt’s predominantly Muslim population.