An own goal by Mohamed Abdul-Rahim in the first-half gave Zamalek the lead before new signing Ahmed Magdi scored his first goal for the club 14 minutes after re-start to ensure the win.
Zamalek's second successive victory put them in fourth place of the league table with six points, three behind leaders Ismaili.
Ittihad's poor start to the new season leaves them second from bottom on just one point. Coach Mohamed Omar is likely to announce his resignation, with Mohamed Salah tipped to be his successor.
Zamalek's Mohamed Aboul-Ella was deployed in the centre of midfield, with Magdi moving to the left flank in an unfamiliar role.
Mostafa Gaafar partnered Abdul-Halim Ali upfront as Amr Zaki was missing after being suspended for one match by the Egyptian Football Association for insulting the referee in Zamalek's match against Al-Baladeya.
Zamalek efforts were tame in the first-half and their sluggish display couldn't help them break through Ittihad tight defense.
Even their opener came through an unlikely source, Ittihad defender Abdul-Rahim.
Zamalek right-back Ahmed Ghanem tricked an Ittihad defender before sending a low cross that was mistakenly converted by Abdul-Rahim into his own net.
The referee then stopped the match for about five minutes due to the fans' angry chants and insults towards EFA vice-president Ahmed Shobeir.
Zamalek supporters believe that Shobeir is totally biased against their club and that he is the one responsible for Zaki's suspension.
Ittihad pushed forward in the second-half searching for the equalizer, leaving gaps in their defense. However, Zamalek threatened Essam Mahmoud net on very few occasions.
Zamalek playmaker Mahmoud Abdul-Razeq 'Shikabala' should have doubled the lead six minutes after the interval when he was released clear on goal by Gaafar's through pass but his hesitation resulted in the ball being easily blocked by Mahmoud.
Moments later, Ali connected with Ghanem's cross at the far post but his weak header was denied by Mahmoud.
Zamalek were awarded a penalty when Gaafar was adjudged to have been brought down by unlucky defender Abdul-Rahim.
Magdi stepped-up and his powerful shot left Mahmoud with no chance.
Ittihad finished with 10 men on the field after Mahmoud Sobhi was sent-off in the dying minutes.
Watch Zamalek's goals: