Olympiacos opened their group campaign with a surprise 3-2 win over La Liga's reigning champions, but were brushed aside 4-0 at the Vicente Calderon on Wednesday as Mario Mandzukic scored a hat-trick after Raul Garcia netted a ninth-minute opener.
Atletico head into the final round-robin match against Juventus, who need a point to take second place out of Olympiacos' reach.
A two-goal victory for the Serie A leaders in Turin would see them pip Atletico to first place and a more favourable seeding for the knockout stages on a superior head-to-head record after Diego Simeone's side were 1-0 winners in the reverse fixture last month.
"There's still another game but we this was an important one after we lost in Greece," Raul Garcia told AS.
"Finishing first in the group was our goal at the start, but we know it will be very complicated to play in Italy."
Raul Garcia believed meticulous preparation and a desire to right the wrongs from their trip to Greece was behind a highly impressive team display on Wednesday.
He added: "The key has been working well. We studied the game very well and knew where to hurt our opponents.
"Everyone depends on the team and we want to be the best team we can be. I scored a goal but I'm not worried about scoring, [I just want to] help the team."
