Smouha's new signee Mohamed Abdel-Aty scored the first goal for Smouha in the 27th minute, before Moroccan winger Abdel-Kabir Wadi scored twice in the 48th and 51st minutes.
Ahly’s defeat left the Reds at the bottom of group six with only three points.
Meanwhile, Smouha raised their total points to seven to lead the group and advance to the next round.
EFA Cup regulations state that each leader of the three groups will qualify to the knockout stage along with the best second placed from all the groups.
Ahly’s South African coach Pitso Mosimane decided to begin the game with his available important players, including Mohamed ‘Afsha’ Magdi, Hussein El-Shahat, Taher Mohamed and the South African striker Percy Taw.
“There are no excuses, but we have players infected with COVID-19, in addition to the fatigue that other players suffer from after their return from participating in the Arab Cup, also the fact that we have players in the Africa Cup of Nations and they suffered severe injuries,” Mosimane told post-match press conference.
"This was not a friendly match and we do not make excuses, but as I said we have players who were not available,” he added.
The Reds are scheduled to participate in the FIFA Club World Cup held in the United Arab Emirates, and their first match will be on 5 February against Mexico’s Monterrey.
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