But Schalke fought back thanks to goals from Jefferson Farfan and Mario Gavranovic either side of half-time before Farfan put on the finishing touches with a late goal to make it 3-1 on the night and 4-2 on aggregate.
With the game evenly poised at 1-1 following the first leg in Valencia, the visitors took the lead in just the 16th minute when Ricardo Costa headed home from close range after some brilliant lead-up work from Mehmet Topal whose shot was deflected in by his teammate for the opener.
However, the Germans hit back when Peruvian Jefferson Farfan curled a free-kick into the top corner to make it 1-1 in the 40th minute before they took the lead 12 minutes later when Mario Gavranovic slid the ball in after a Farfan shot, the ball hitting both posts before falling in.
Valencia attempted to pull themselves back into the contest but were unable to pierce the Schalke defence as Raul went about trying to wrap up the match against some of his countrymen but it took Farfan to add a third when he was free on goal in injury time and slotted past Vicente Guaita to end it all for the Spaniards.
Schalke Manuel Neuer (gk) - Atsuto Uchida, Benedikt Howedes, Per Metzelder, Sergio Escudero - Jefferson Farfan, Peer Kluge (Sarpei 82'), Joel Matip (Papadopoulos 60'), Jose Manuel Jurado (Draxler 76') - Raul, Mario Gavranovic
Valencia Vicente Guaita (gk) - Bruno Saltor, David Navarro, Ricardo Costa, Jeremy Mathieu - Ever Banega (Costa 71'), Mehmet Topal, Joaquin Sanchez, Pablo Hernandez (Soldado 64') - Juan Mata, Aritz Aduriz (Jonas 75')