Schalke retained top spot in Group B courtesy of their victory away to Benfica, who go into the Europa League, with Lyon progressing in second place following their 2-2 home draw against rock-bottom Hapoel Tel-Aviv.
Schalke took the lead in Portugal in the 19th minute with Jose Manuel Jurado firing beyond Roberto after good work from Raul Gonzalez and Ivan Rakitic.
And they made sure of progress as victors of the group in the closing stages when Benedikt Howedes found the net nine minutes from time, with Luisao's late response for the hosts little more than a consolation.
Substitute Alexandre Lacazette's late goal denied Hapoel Tel-Aviv a place in the Europa League and ensured Lyon would finish in second place.
Lisandro Lopez put the hosts in front just after the hour mark only for the Israeli outfit to respond immediately through one-time Chelsea forward Ben Sahar.
And the home side were stunned just six minutes later when Eran Zahavi produced a moment of acrobatic brilliance to leave goalkeeper Hugo Lloris with no chance.
A 2-1 victory would have seen Eli Gutman's men edge ahead of Benfica, but with just three minutes remaining Lacazette's effort crushed their hopes.
FC Copenhagen qualified for the knockout phase behind Group D winners Barcelona courtesy of their 3-1 victory over Panathinaikos, with Pep Guardiola's men seeing off Rubin Kazan at Camp Nou as the visitors had to settle for the Europa League.
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