Jesualdo Ferreira's side made a powerful start with in-form Argentine forward Sebastian Leto scoring twice in the first half.
Leto's first came after he raced on to Greece midfielder Kostas Katsouranis' pass and lifted the ball over Giannis Arambatzis.
Leto then doubled the lead with a precise, low finish before Katsouranis made it 3-0 eight minutes after half-time from close range.
AEK fought back with Steve Leo Beleck volleying in from a Pantelis Kafes knock-down just after the hour mark before Leonardo set up a tense finish with a sweetly-struck curling shot with one minute of normal time remaining.
Panathinaikos held on though to take a win which saw them move two points clear of Olympiakos Pireaus with 19 points from seven matches heading into the international break. AEK, who have played eight matches, lie fourth with 13 points.
Ernesto Valverde's Olympiakos bounced back from Tuesday's 1-0 defeat to Borussia Dortmund in the Champions League with a 3-2 win at Aris Salonika on Saturday.
The weekend's results set up an enticing derby clash between the two leading clubs with Olympiakos hosting Panathinaikos at the Georgios Karaiskakis stadium on November 19.
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