Striker Salah Mohsen found the net just a minute before halftime, seizing upon a precise assist from winger Abdel-Rehim Daghmoum to control the ball in the area and slot it home.
Midfielder Mohammed Al-Shiteewi leveled the score for Al Hilal five minutes before the break with a powerful strike from outside the box.
Mohsen restored Masry's lead in the 63rd minute with a well-placed shot in the box.
Al-Hilal's captain, Faisal El Badri, headed in the equalizer in the 68th minute from a sharp cross outside the area.
Al-Shiteewi then clinched the vital win for Al Hilal with a header from close range just ten minutes before the final whistle.
Despite Masry coach Ali Maher making three substitutions to salvage a draw, including new signing Khaled El-Ghandour, Tunisia's forward Fakhreddine Ben Youssef, and talented midfielder Hussien Faisal, Al Hilal's defense held firm, securing a 3-2 victory.
Masry earned a spot in the continental competition after finishing fourth in the Egyptian League last season, while Al Hilal qualified following a dominant 5-1 aggregate win over Uhamiaji FC of Zanzibar in the previous round.
The return leg is scheduled for next week in Port Said.
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