Defensive gaps were exposed by a clinical Atletico side as goals from Gleison and Vidinho gave the visitors a surprise 2-0 half-time lead.
Zamalek were guilty of squandering a hatful of clear-cut chances in both halves, hitting the woodwork three times.
They finally found the net when substitute Youssef 'Obama' Ibrahim halved the deficit 12 minutes into the second half before defender Mahmoud El-Wensh secured a share of spoils with a deflected strike five minutes into the additional time.
Morocco's Wydad top Group D with three points after crushing Angola's Sagrada Esperanca 3-0 on Friday, with Zamalek and Atletico gaining one point each.
Atletico stunned the home crowd on 22 minutes when lively winger Jaredi Teixeira outpaced left-back Ahmed Fattouh, who put on some impressive shows with Egypt at the African Nations Cup, down the flank before crossing low for the unmarked Gleison to bury the ball into the bottom corner.
El-Wensh headed against the bar and Fattouh hit the side netting when two of his teammates were in a good position to score as they pushed forward in search of an equaliser, but they were caught napping again when Petro added a second on 35 minutes.
Vidinho found himself completely unmarked after a free kick was floated in from the left to side-foot home, although television replays suggested that he was in an offside position. VAR technology is only introduced in the Champions League knockout phase.
Zamalek then assumed complete control, missing some gilt-edged chances.
Winger Ahmed Zizo rattled the bar with a powerful shot on the turn before the second-half introduction of Obama and veteran winger Mahmoud Shikabala further energized Zamalek's attack.
Moroccan winger Achraf Bencharki had a low shot from the edge of the area denied by the post after a square pass from Obama, who also headed over the bar with the goal at his mercy shortly after.
A superb Bencharki lob forced a great reflex save from keeper Wellington before Obama finally made Zamalek's dominance count in the 57th minute.
He exchanged passes with Shikabala twice to jink into the area and beat Wellington at his near post with a low shot that took a slight deflection.
A defensive error from El-Wensh could have cost Zamalek though as he was dispossessed by Teixeira, whose attempted lob was collected by Egypt keeper Mohamed Abou-Gabal.
But El-Wensh stole the show at the death when he collected a pass from substitute Razack Cisse in the area before hitting a low shot that deflected off a defender and looped into the net past the desperate attempt of defender Pedro Pinto to clear it, denying Atletico a famous win.
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