The Colombian coach had been frustrated in his debut against Arab Contractors after being held to a late 2-2 draw last week, but this time Tunisian striker Seif Jaziri secured the win for the White Knights, who are battling for second place in the league table.
The defending champions currently sit in fourth place with 43 points, six points behind second-placed Future FC and ten points behind league leaders Ahly, who still have four matches in hand.
Both sides played an open game, with Zamalek earning an early lead in the 11th minute when Tunisian striker Seif Jaziri rose above his marker to meet Ahmed 'Zizo' Sayed's cross and delivered a nice header to score.
The White Knights had the chance to double their lead, but Youssef Nabih and Zizo missed two easy opportunities. They nearly paid for their lack of cutting edge when Ceramica Cleopatra's Mohamed Fathi missed a chance to equalise in the 33rd minute with the goal at his mercy.
In the second half, Osorio made four substitutions to inject fresh energy into his side, which continued to squander a number of easy chances. Meanwhile, the visitors missed several opportunities to level the score as Zamalek's defense remained vulnerable.
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