Saied Mourad gave the hosts an early lead when he capitalized on some poor marking by Zamalek defender Amr Al-Safti.
Two late goals from left-back Sabri Rahil and substitute Shikabala handed the improving Zamalek their second successive victory.
The victory moved the White Knights into sixth place of the league table on 33 points.
Struggling side Olympic, who edged closer to relegation, remained second from bottom with 20 points, five behind the safety zone with six matches to go.
No Support
Although Olympic played at home, they did not enjoy any support from the crowd.
Zamalek fans were the ones who filled the 20,000-seat Alexandria Stadium, which will be closed for renovations as Egypt will host the U-20 World Cup in September.
The Cairo giants were buoyed by their convincing 4-2 victory over Gaish but saw themselves fall behind to Mourad's goal after 10 minutes.
The 25-year-old midfielder cut ahead of Al-Safti to shoot goalwards but his initial effort was parried by Zamalek keeper Abdul-Wahed Al-Sayed. He made no mistake at the second attempt.
Zamalek then laid siege to Olympic's area and dominated possession as the hosts packed their players behind the ball in a bid to keep their lead intact.
The efforts of Mohamed Helmi's men bore fruit in the first period as Zamalek failed to pose threat.
Zamalek coach Michel Decastel introduced star winger Shikabala, who started the game on the bench, instead of ineffective playmaker Alaa Ali.
Shikabala's energetic moves bothered Olympic's defense but he still gave away too many passes.
Striker Sherif Ashraf, who scored a brace against Gaish, almost equalized for Zamalek two minutes after the restart but his header from Rahil's cross struck the woodwork.
He had another glorious chance shortly after when he was picked out unmarked by a low cross from in-form right-back Hazem Emam but his mis-hit shot missed the target from six yards out.
Ashraf, who was not at his best, made way for January arrival Mohamed Al-Morsi, who is yet to open his Zamalek account.
Stunning Volley
Zamalek needed a piece of magic to break down Olympic's stubborn defense eight minutes from time.
Olympic defenders poorly cleared a corner and Rahil pounced to fire a stunning left-footed volley from the edge of the area that left Mahmoud Al-Sayed with no chance.
It was his first goal since joining Zamalek in the January transfer window.
The spectators erupted into ecstasy when Shikabala put Zamalek ahead just one minute later.
Emam latched onto a through ball and raced into the area but his shot was blocked by Al-Sayed.
Despite the desperate attempts of Olympic defenders to clear the danger, Shikabala slotted into an empty net to give Zamalek all three points.