The Cairo giants' eccentric chairman Mortada Mansour failed in his efforts to change the team's home venue after a lengthy winless run in all competitions that he blamed on a pitch hoodoo.
But Zamalek finally laid the stadium's ghosts to rest, although they were not so convincing.
Moroccan winger Achraf Bencharki, who is unlikely to extend his deal after it expires at the end of the season, gave Zamalek a first-half lead after a fine give-and-go with left-back Abdallah Gomaa.
Defender Baher El-Mohammadi brought Ismaily level with a penalty on 61 minutes but substitute Omar El-Said made an instant impact after coming on, heading home with his first touch two minutes later to give Zamalek all three points.
Zamalek lead the table with 44 points, four ahead of second-placed Pyramids FC and seven clear of perennial rivals Ahly, who still have four matches in hand.
Struggling Ismaily, the three-time league winners who face the unthinkable prospect of being relegated to the second division, lie third from bottom with 18 points.
Zamalek coach Jesualdo Ferreira stuck to the same 3-4-3 scheme that he adopted in the 2-1 Egypt Cup win over Aswan last week, but the team still found it difficult to carve out openings.
Ismaily sat back and tried to hit Zamalek on the break, but the hosts were barely troubled at the back.
Chances were at a premium in a poor first half that only sprang to life when Bencharki opened the scoring three minutes before halftime.
He fed the overlapping Abdallah Gomaa, who deputized for the injured Ahmed Fattouh, and jinked into the area to receive the left-back's cut-back and slide the ball into the bottom corner.
Ismaily were awarded a penalty out of the blue when Zamalek's central defender Mahmoud Alaa was adjudged to have pushed an opponent as they challenged each other for a cross, with El-Mohammadi firing down the middle to level the score on 61 minutes.
However, El-Said quickly restored Zamalek's lead when he rose above his marker and sent a superb glancing header into the far corner following an inviting free-kick from winger Ahmed Zizo.
Zamalek then remained in control and were unlucky not to extend their advantage on a couple of occasions, with Alaa heading just over the bar and midfielder Emam Ashour rattling the post with a powerful shot from the edge of the area.
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