The former champions travel to the Spanish capital knowing only victory over Atletico Madrid would be enough, and even that would be insufficient if second-placed Zenit St Petersburg were to beat Group G's bottom side Austria Vienna.
Atletico are tied on 40 points with Barcelona at the top of the Spanish league having dropped only five points all season, and none at home.
They have won both their home European matches as well, but Porto coach Paulo Fonseca is adamant victory is not an impossible task.
He told a press conference: "Atletico Madrid have made a thunderous start to the season. They have only lost one game and drawn one and this attests to their value as a team.
"But we have no other outcome than victory. We have no choice to move to the next stage. We are here with the ambition to beat Atletico Madrid."
Fonseca is taking heart from his side's record in the group so far, with four of their five points coming away from home.
He said: "We did not win any games at home and abroad we have made a positive campaign.
"First, we have to worry about us, and only then think about the other game. If we do not win our game, the other does not matter."
Atletico's only dropped points so far came last time out when they drew 1-1 with Zenit in Russia.
Midfielder Mario Suarez, who will miss the game with a knee injury, insisted his side would not be taking things easy.
He said on clubatleticodemadrid.com: "We are taking things game by game. This is how we are getting the results we've had and that's how we must continue.
"On Wednesday, we have an important Champions League match against Porto. We're going to go out to win and on Sunday, too, against Valencia. That's our mentality and we hope that in May we will be fighting for great things."
Fonseca hopes midfielder Lucho Gonzalez will be fit for the clash while Atletico full-back Juanfran misses the game through suspension.