奈阿波利斯馬克多尼科斯

The association was founded in 1928, and the name means 'Macedonian'. At the time of its formation, the club's original name was Prosfygiki Enosis (Refugees Union - the founders were Greek refugees who came from Turkey after the 1922 war disaster) ^[] but they were forced to change it in 1936 after the Metaxas government suggestion.^[] The team's name inspired many regional teams. As a result, there are more than twenty Macedonian teams who also use it (Olympiacos and PAOK are also common names for Greek football clubs).

The club's best moments were in the 1940s when the team was struggling for the Greek Championship (1947) but didn't make it and in the 1980s when Makedonikos took part in the Super League (1st Division Championship) (1982–83) and was relegated after a play-out match against Panionios (3-2 final score). Makedonikos still stands out as the only Greek team who managed not to be beaten by Olympiacos (0-0 in Efkarpia and 1-1 in Karaiskakis Stadium). They also managed not to lose a game in Efkarpia against PAOK (0-0), Aris (1-0), Iraklis (0-0), AEK (1-0), Panathinaikos (3-0), the most famous clubs of the Greek League. They also made it to the 1980 Greek Cup semi-final, where they were eliminated by Kastoria F.C., who finally won the Cup. Makedonikos F.C. was also one of the strongest clubs in the 2nd Division from the late 1970s to the early 1990s. In 2008, they ascended to the national league after fourteen years of absence with Marcelo Zuleta as technical director. In 2016, the club won the EPSM Cup by winning 2-1 in the final at Toumba Stadium and were also champions of the EPSM A1 Division, having lost only twice. In the play-off match against Apollon Paralimnio (which was crucial for both teams' promotion), chairman Pavlos Andronis withdrew the team due to bad arbitration, so the team lost their chance to be promoted. However, during the 2016-17 season, Makedonikos finished on top of the league and was promoted to the Third National Division (Gamma Ethniki), having won the play-off match against Olympiacos Kimina (3-1).

Many great Greek football players joined Makedonikos F.C. over the years. Giorgos Karamihalos, Fanis Tountziaris, and Nikos Sakellaridis made their name wearing the green shirt of Makedonikos while other famous footballers played in Efkarpia sometime in their career. Giannis Damanakis, Giannis Gounaris, Christos Giannakoulas, Kostas Iliadis, Arthur Beltsos, Theodoros Apostolidis, Thanasis Beltsos, Grigoris Fanaras, Panagiotis Kermanidis, Kostas Drambis, Kostas Tsironis, Giorgos Koulakiotis, Takis Nikoloudis, Christos Terzanidis, Giorgos Polyzoidis, Michalis Iordanidis are some of them.