After champions Panathinaikos had cut the lead to two points by defeating Xanthi 2-0 on Tuesday, the pressure was on Olympiakos but midfielder Fuster eased their nerves by putting the hosts in front after 32 minutes.
After Iraklis had Algerian forward Karim Soltani dismissed for a second bookable offence in the 73rd minute, striker Pantelic sealed the victory for Olympiakos with his goal seven minutes from time to move Ernesto Valverde's team on to 39 points after 16 games.
Olympiakos announced the signing of 24-year-old Greece defender Giannis Maniatis on Wednesday, on a three-and-a-half-year contract from Panionios.
PAOK Thessaloniki remain in third spot on 24 points after playing out a 1-1 draw at strugglers Panserraikos.
Greece international striker Dimitris Salpigidis gave PAOK the lead in the second minute but the hosts struck back through Giorgos Georgiadis in the 72nd.
AEK Athens missed out on the chance to leapfrog PAOK when they were held to a goalless draw at home to Kerkyra.
Panionios, who were expected to announce the transfer of Greek international forward Kostas Mitroglou and Manolis Moniakis from Olympiakos as part of the Maniatis deal, remain in trouble near the danger zone after a goalless draw at eighth-placed Olympiakos Volos.
The Nea Smyrni club lie second from bottom with 16 points.
