[4] Due to the Young Turks' revolt of 1908 and their promises for ease of ethnic tensions in the area, the club was forced to change its name.

[5] Iraklis won Alliance 3–1, Progrès Sportive 5–1 and after winning the French-German School Alumni Union, the club was proclaimed Champion of Thessaloniki.

[7][8] In the following season Iraklis celebrated its consecutive win in the Macedonia Football Clubs Association Championship but failed to qualify for the National final.

In 1965, Kostas Aidiniou, a player that together with fellow Greek international Zacharias Chaliabalias would lead the club for the following decade, debuted for Iraklis.

[9] In the 1970–71 season Iraklis, under the guidance of Yugoslav manager Ljubiša Spajić, finished 5th in the league, the club's best positioning since the establishment of Alpha Ethniki.

[11] On 22 November 1975, the club acquired Vassilis Hatzipanagis, a USSR national of Greek descent, who was late voted a Greece's Golden player for UEFA Jubilee Awards.

[11][19] Iraklis improved slightly in the next season ending up ninth in the league with Gesios achieving a personal best scoring 13 goals.

[11] Iraklis finished sixth in the league, had a positive goal aggregate for the first time since the 1973–74 season and achieved the club's biggest victory in Alpha Ethniki by beating Rodos by an 8–1 margin.

[22] In the Greek Cup competition of the season Iraklis eliminated Veria, Niki Volos, Almopos Aridaea and Panarkadikos to reach the semi-finals.

[23][24] Iraklis proceeded to play in the Cup final, but as the players' morale was damaged the club was defeated by underdogs Kastoria by a 5–2 margin.

[26] Upon its return to the top tier Iraklis managed to finish in the 6th position in the league and achieved the club's best goal difference at the time with +14.

[32] Two years later, 17,000 fans travelled to Athens to support Iraklis in the 1987 Greek Cup final, unfortunately to see their team lose 3–1 on penalties (1–1 regular time) to OFI Crete.

Despite the acquisition of many promising players during the first summer, the 2000–2001 campaign didn't have the expected results, with the club finishing in 5th position, out of European qualification spots.

Next summer, Mytilineos's first move was to sell the highly rated striker and fans' favorite Michalis Konstantinou to Panathinaikos, setting a new record for the highest fee received for a domestic transfer.

[34] After a 5-month period during which Houlis controlled the team, the Greek football commission finally annulled the transfer, raising questions in the media regarding its handling of the previous one between Mytilinaios and Spanoudakis, too.

During the 2005–06, he led Iraklis to an acclaimed 4th-place finish, playing effective and attractive football, creating a club record for 13 consecutive wins at home.

However, with considerable debts to players, coaches and the state, Spanoudakis started the 2006–07 season attempting to reconcile Iraklis finances by selling Joël Epalle and Panagiotis Lagos, who were instrumental in the previous year's success.

Next year Kofidis resigned as manager of a considerably weakened team after Iraklis lost 7 and drew 2 of his first nine games in Greek Super League and additionally was eliminated from the UEFA Cup in extra time by Wisła Kraków.

On 23 January 2012, the team played their first game at home against Tilikratis, while pending approval of the merger by the Greek Professional Sports Committee.

Iraklis was relegated in 2019 from the professional second-tier Football League into the amateur fourth-tier Gamma Ethniki, due to the restructuring of the Greek national championships and its performance in conjunction to its financial state.

At the same time, the coach Sakis Tsiolis and the football players of the team asked Stratos Evgeniou to be paid with less money in order to collect the necessary financial amount.

Within 3 working days, the required financial amount was collected by the fans of Iraklis Thessaloniki and finally the repayment of the former football player of the team was achieved.

[49] In 1915, Iraklis rented an area in the centre of Thessaloniki for a ten years period, but the club was unable to use its facilities until 1919, due to World War I.

The training facilities include three football fields, gym, sauna, water pool, such as the administration building of Iraklis FC.

[58] On 24 January 1971 Iraklis set the highest attendance record for any football match in Alpha Ethniki, with 45,634 tickets sold in the club's contest against Panathinaikos.

[73] In 2007 Spanoudakis declared the club's inability to repay its debts to the players and tried to hand Iraklis' stocks to Cypriot businessman Pheevos Morides.

[78] On 10 July 2007 Iraklis' administration building was set on fire by supporters in an attempt to express their discontent for the cancellation of the club's takeover from Antonis Remos.

Two years later, despite successfully retaining Super League status once again by finishing 12th the team was again relegated to gamma ethniki (third tier) while the financial situation of the club was again under severe deterioration.

This urged Papathanasakis, on 7 September 2017, to declare Iraklis' inability to satisfy financial obligations, causing the club to be disbanded for the second time in five years.

In the summer, negotiations began on the purchase of the football section of Iraklis Thessaloniki by the Greek–American businessman Tom Papadopoulos, who is involved in the processing and marketing of marble in the United States of America.