Ittihad's hopes to remain in the top flight vanished on Sunday after a 2-2 draw with Egyptian Premier League contenders Zamalek sent them down for the first time since 1960.
Fellow Alexandria-based club Smouha and Arab Contractors were also relegated after 2-2 draw with Ahly and 1-1 draw with Masry respectively.
Ittihad remain at the bottom with 24 points, seven points behind the safety zone with just two matches remaining. They suffered relegation for the third time in their history after a poor season.
The six-time Egyptian Cup winners, who were founded in 1906, were also affected by a persistent financial problem.
One-time league winners Arab Contractors, who lie second from bottom with 24 points, went down after a goalless draw with Masry.
Smouha took a shock two-goal lead over league leaders Ahly, who roared back in the dying minutes to score twice, including a goal from defender Ahmed El-Sayed deep in stoppage time.