With a third-place finish already secured, Schalke will be joining champions Borussia Dortmund and Bayern Munich in next season's Champions League draw.
Schalke took the lead just after the half-hour at Veltins-Arena through Dutchman Klaas-Jan Huntelaar, but were forced to wait until the final 20 minutes to seal the win.
Lewis Holtby doubled their lead on 73 minutes, with Raul Gonzales and Huntelaar netting in the final six minutes.
Elsewhere, Dortmund won 5-2 at relegated Kaiserslautern, while Bayern Munich defeated Stuttgart 2-0.
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