The hosts took the lead after nine minutes through a goal from Senegalese striker Baba George.
Winger Mohamed Abdul-Shafi leveled the score eight minutes later with a superb first-timer after being set-up by defensive midfielder Ahmed Abdul-Raouf.
Abdul-Raouf turned from provider to scorer to put Zamalek in front on 30 minutes and Shikabala wrapped up the victory with a brilliant solo effort in stoppage time.
The Cairo giants also came from behind to defeat Bani Yas' compatriots Al-Ain 2-1 on Monday.
They are holding a training camp in the UAE in a bid to return to league action in the best possible way after stuttering in the early stages.
Zamalek, who line ninth in the 20-team table, bagged just seven points from their first six games.
They have won once and lost twice since Frenchman Henri Michel replaced Michel Decastel as the team's head coach.