The defeat by Ahly proved the last straw, with Gonias shown the door despite penning a three-year contract extension in August last year.
"We would like to thank Takis Gonias and his backroom staff for the time they spent in charge of the football team," Pyramids said in a brief statement on their social media channels.
Pyramids had territorial dominance against Ahly but were caught on the break as the Red Devils ruthlessly punished their slack defending.
It marked their third loss in their opening 11 league games as they slipped to fourth in the table with 20 points, seven adrift of leaders Ahly.
Gonias took over as Pyramids coach for a second spell in April last year, helping them finish as runners-up in the league for their best ever position.
He also took charge of the club for three months in 2021.
Local reports said former Zamalek coach Jaime Pacheco is the frontrunner to succeed Gonias as Pyramids seek to rescue their faltering season.
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