The Bundesliga outfit showcased their European pedigree to upstage their opponents on the night, standing them in good stead for the rest of their group stage adventure
Goals from Benedikt Howedes and Klaas-Jan Huntelaar sealed the tie, with the Greeks netting scant consolation with a single goal from Djamel Abdoun.
Despite the frenzied atmosphere created by the home fans, the opening half proved to be a dour, cagey affair, with either team cautiously probing forward to test for tell-tale signs of their opponents' weaknesses.
Paulo Machado signalled the Greek Superleague champions' intent when he advanced confidently down the left in the fifth minute, but Euro 2012 revelation Kyriakos Papadopoulos was on hand to head clear the danger against his former employers.
Spurred on by the cauldron of home support, Olympiakos continued to search for avenues to break into their visitors' area, as Rafik Djebbour narrowly missed connecting with captain Vasilis Torosidis' searching cross. Schalke were not content to let the Greeks have it all their way however, as Netherlands international Huntelaar gave keeper Balasz Megyeri a reminder that his team were very much on the pitch with a headed half-chance in the 17th minute.
Olympiakos were not to be rattled, and Jose Holebas sent a free-kick from distance inches wide of the post. Portuguese midfielder Machado was giving Schalke counterparts Jermaine Jones and Roman Neustadter the run-around, capping off a solid start to the game by whipping an excellent cross to Djebbour, who escaped the attentions of his marker to blast just wide.
The close shave only served to jolt Huub Stevens' men into action, cumulating in a move that saw Christian Fuchs round off a spate of pressure by exploiting the hosts' insecurity in defending the flanks, launching a ball into the area that was cleared with some difficulty by Francois Modesto.
Schalke skipper Howedes had the pleasure of being the first man added to the referee's book, picking up a yellow card for rough-housing with Machado in the centre of the pitch in the 30th minute. Nevertheless, The Royal Blues persisted in stamping their mark on the game, and it was via a foray forward that a moment of controversy occurred.
Papadopoulos thought he had earned Schalke the opener when he rose to challenge Megyeri for a ball, subsequently depositing it in the back of the net, but the match official disallowed the goal for a supposed infringement by the Greece international. The Bundesliga side were not to be denied for long though, and Howedes rose highest from a corner to truly gift his side the lead in the 41st minute.
With the goal serving to galvanise the German's spirits, Schalke emerged from the half-time break with increased potency, nearly doubling the scoreline when Megyeri fumbled a routine cross into the path of summer signing Tranquillo Barnetta, who from ten yards somehow managed to blaze the ball high over the bar.
It was Olympiakos' turn to show they would not yield in front of their own fans now, as Joel Matip's poor attempted clearance fell to Djebbour, who subsequently saw his goal-bound effort cleared off the line by the recovering Cameroon international.
The ensuing chaotic play suddenly led to Leonardo Jardim's outfit drawing level in the 58th minute in bizzare manner, after a long punt from goal was contested but missed by either of Howedes and Djebbour, enabling Abdoun to sweep home in the easiest of manners.
As momentum in the match continued running high, Huntelaar, who had been well shackled to that point, immediately handed his team the initiative again once play restarted. A blindingly quick avenue into Olympiakos' box paid dividends, as the hitman clinically settled matters.
The former AC Milan striker then went from hero to villain, missing a penalty after Barnetta was brought down in the box following his sublime piece of skill. Huntelaar stepped up to take the spot-kick, but beat Megyeri, only to see the ball come off the post.
Barcelona loanee Ibrahim Afellay came on to lend some cutting-edge as Schalke poured forward in a bid to seal the match for good, but some alert goalkeeping foiled Huntelaar at close range, after Jones had put him in in the 85th minute. With the home side realising all was lost, the match slowed to walking pace.
Schalke's win puts them in good stead for the rest of the group stage. Olympiakos turn out against Arsenal in their next Group B fixture.