After playing with the youth teams of the Greek clubs Asteria Academy and Aris, Mitoglou played for the first time in Greece's top-tier level, the Greek Basket League, with the senior men's team of Aris Thessaloniki, during the 2013–14 season.

Mitoglou played 3 years of NCAA Division I college basketball at Wake Forest from 2014 to 2017.

He then moved to Wake Forest University,[6][7] but Aris retained his club rights, through the year 2017.

After leaving Wake Forest, Mitoglou signed a 4-year contract with the Greek club Panathinaikos.

[11][12][13] On June 25, 2021, Mitoglou signed a two-year deal with Italian powerhouse Olimpia Milano worth 1.8 million Euros.