The Cameroon international has penned a three-year deal at the Veltins-Arena.
Choupo-Moting scored 20 goals in 74 Bundesliga games for Mainz after joining the club from Hamburger SV in 2011.
"I'm delighted that Eric Maxim has decided to sign for us," sporting director Horst Heldt told Schalke's official website. "He is very versatile, but first and foremost our plan is to use him in a central, attacking position."
Choupo-Moting has scored 12 goals in 26 appearances for Cameroon.