Spanish coach Michel's revamped team, who won their 40th domestic league title last season, began the match with seven new players in the starting XI including Argentina forward Javer Saviola, signed from Malaga last month.
However, it was one of last season's regulars, Greece midfielder Giannis Maniatis, who proved the difference by scoring the only goal of the game when he side-footed home after a corner in the 61st minute.
Olympiakos looked more dangerous after the introduction of exciting young Greece winger Giannis Fetfatzidis after halftime, but he failed to inspire the visitors to more goals.
Forwards Kostas Mitrogou and Joel Campbell, as well as Fetfatzidis himself, each missed chances to add to the scoreline.
The victory ensured the Red and Whites kept level with Panathinaikos, who won 2-0 against Panaitolikos in their season opener 24 hours earlier.