Mantzaris began his professional career in the Greek 2nd Division with Peristeri, the team of his hometown.

On September 5, 2011, Mantzaris signed a four-year deal with the top-tier level Greek Basket League and EuroLeague club Olympiacos Piraeus.

[1] He won both the EuroLeague and Greek League championships in 2012, being a useful tool for the team of coach Dušan Ivković, especially due to his defensive ability.

[2] Despite suffering the knee injury, he remained close to his teammates both in and out of the locker room in order to support them, as they won the EuroLeague 2012–13 season championship.

Mantzaris returned to action seven months later and in early October of the same year won the FIBA Intercontinental Cup against Pinheiros at Ginásio José Corrêa, Brazil.

[4] On July 20, 2019, Mantzaris was released from Olympiacos, after eight seasons, and signed with UNICS Kazan of the VTB United League and the EuroCup, playing under fellow Greek coach Dimitrios Priftis.

[8] After the season ended, Mantzaris stated that the cooperation with coach Aris Lykogiannis was not good, something that confirmed the poor communication between them.

On March 24, 2023, Mantzaris signed with Venezuelan club Panteras de Miranda for the rest of the season.