Alejandro Dominguez, Alan Pulido, Esteban Cambiasso and Kostas Fortounis all found the target, inspiring a welcome return to winning form for Olympiakos after they suffered their first defeat of the season at AEK Athens the previous week.
Marco Silva's reigning champions, now on 64 points, extended their lead to 18 points over second-placed AEK, and the Red and Whites can, mathematically, wrap up the title with three points from next week's home match against strugglers Veria.
In the day's big 'North versus South' derby, third-placed Panathinaikos were held to a thrilling 2-2 draw by 10-man PAOK Salonika at the Apostolis Nikolaidis Stadium in Athens.
Panathinaikos delighted the home fans when they built a 2-0 lead courtesy of Sweden striker Marcus Berg's 10th-minute opener and a strike from Nikos Kaltsas six minutes into the second half.
Yet a contender for goal of the season from Bosnia-Herzegovina midfielder Gojko Cimirot, who smashed home a superb long range drive after 56 minutes, gave PAOK hope.
With 23 minutes left, Dimitris Pelkas then grabbed the equaliser but his team mate Haris Harisis was dismissed in added time after picking up a second yellow card as PAOK clung on for the point which moves them up to fourth on 35 points, but still seven points behind Panathinaikos.
(Editing by Ian Chadband)
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