The 25-year-old, who was part of Cameroon's FIFA World Cup squad, has signed a three-year deal at the Veltins Arena.
Choupo-Moting scored 20 goals in 74 Bundesliga appearances for Mainz and joins a side that will compete in the UEFA Champions League.
"I am delighted that Eric Maxim has decided to join us," Schalke chief executive Horst Heldt told the club's official website.
"He is versatile, but we plan to use him first and foremost in a central offensive position."
Choupo-Moting has plenty of experience in the Bundesliga, having come through the youth ranks at Hamburg.
He spent the 2009-10 campaign on loan at Nurnberg, before linking up with Mainz in May 2011.