The world champion was 0.393 seconds quicker than team-mate Nico Rosberg, with Ferrari's Sebastian Vettel 0.938secs off the pace in third place.
Mercedes seem to have a huge advantage over Ferrari, who have a smaller but clear edge over Williams and Red Bull.
Williams' Valtteri Bottas and Felipe Massa were next, ahead of Red Bull's Daniel Ricciardo and Max Verstappen.
Hamilton, fresh from his superb effort in finishing third from the back of the grid in Belgium last weekend, was in crushing form throughout the final hour of practice in warm sunshine at F1's most historic circuit.
He was just under 0.2secs clear of Rosberg in second practice on Friday and doubled that margin on Saturday morning.
Even at this early stage, the race victory looks likely to be a private battle between Hamilton and Rosberg, with Ferrari nowhere near the world champions despite introducing their final engine development upgrade of the season in an attempt to close the gap.
Hamilton is nine points clear of Rosberg heading into the grand prix, with eight races remaining this season.
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Ferrari are also said to have some concerns about the reliability of the new engine, having rushed it through to introduce it in time for their home race.
Force India's Sergio Perez was ninth, ahead of Haas' Esteban Gutierrez, whose team-mate Romain Grosjean had a spin early in the session and was beached in the gravel trap at the Ascari chicane.
McLaren's fears that they will struggle to be in the top 10 on the grid on this power circuit are coming true - Jenson Button was 12th fastest behind the second Force India of Nico Hulkenberg and Fernando Alonso was down in 17th after not putting together a lap on his qualifying simulation run on the super-soft tyres.
Qualifying is live on the BBC Sport website from 12:00 BST and on BBC Radio 5 live sports extra from 12:55.
Italian Grand Prix final practice results
Italian Grand Prix coverage details
Lewis Hamilton was in scintillating form as he dominated final practice at the Italian Grand Prix for Mercedes.