The first training session for the season took place on 11 June 2012 at APOEL's training centre. On 23 June 2012, the team flew to Obertraun in Austria to perform the main stage of their pre-season training and returned to Cyprus on 7 July 2012. During the pre-season training stage in Austria, APOEL played four friendly matches against Blau-Weiss Linz, MFK Košice, SK Sturm Graz and SV Ried. APOEL lost 1–2 by Blau-Weiss Linz, drew 1–1 with SK Sturm Graz and won MFK Košice by 2–0 and SV Ried by 3–2.

On 3 September 2012, APOEL opened their competitive season with a 0–5 win at the Tasos Markou Stadium against Enosis Neon Paralimni. Aldo Adorno scored a hat-trick, while Gustavo Manduca and Constantinos Charalambides scored two more goals for APOEL. On 16 September 2012, APOEL hosted Doxa Katokopias at GSP Stadium, in a match which was played behind closed doors. APOEL won 3–1, with Aldo Adorno scoring twice and Efstathios Aloneftis adding another one to the scoreline. On 22 September 2012, APOEL won 1–3 Alki at Larnaca, with Mario Budimir, Gustavo Manduca and Aldo Adorno scoring one goal each. On 30 September 2012, APOEL beat Apollon Limassol 1–0 at home, with Aldo Adorno scoring the winning goal in the 79th minute. On 7 October 2012, Omonia hosted APOEL at GSP Stadium in a match which ended in a goalless draw. On 22 October 2012, APOEL won Olympiakos Nicosia at home by 4–0, with two goals from Nuno Morais and one goal from Aldo Adorno and Gustavo Manduca. On 27 October 2012, APOEL beat Nea Salamina at Ammochostos Stadium by 0–3. Hélio Pinto opened the score in the first half and Efstathios Aloneftis who came on as a substitute scored twice in the second half. On 5 November 2012, APOEL's impressive run continued by winning Ayia Napa 4–1 at home, with a hat-trick from Aldo Adorno and a goal from Gustavo Manduca. On 11 November 2012, Aritz Borda's goal gave APOEL a narrow 0–1 win over Ethnikos Achna at Dasaki Stadium. On 18 November 2012, APOEL suffered its first league defeat after losing 1–2 at home to AEK Larnaca and fell out of first place for the first time during the season. Albert Serrán opened the score in the first half and Hélio Pinto equalised early in the second half before Jason Demetriou score the winner for AEK. On 26 November 2012, APOEL beat reigning champions AEL Limassol by 1–3 at Tsirion Stadium and became the first team which won AEL this season. Hélio Pinto opened the scoring in the 4th minute and AEL equalised ten minutes later but Gustavo Manduca in the 23rd minute gave APOEL the lead again. Despite APOEL was playing with ten players for almost 30 minutes after Aritz Borda was shown the red card in the 64th minute, Constantinos Charalambides scored a third goal ten minutes before the end to give APOEL a very important victory. On 2 December 2012, APOEL beat AEP Paphos by 0–2 at Pafiako Stadium, with two goals scored from Gustavo Manduca and Selim Benachour. On 8 December 2012, APOEL suffered its second league defeat, losing 0-1 at home to Anorthosis and remained in second place, four points behind leaders Anorthosis. On 15 December 2012, Aldo Adorno's goal in the 76th minute gave APOEL a narrow 1–0 home win over Enosis Neon Paralimni. On 22 December 2012, APOEL won 0–3 at Doxa Katokopias, with Gustavo Manduca scoring twice in the first half and Aldo Adorno scoring another one in the second half. On 6 January 2013, APOEL drew 1–1 with Alki Larnaca at home, with a last-minute equalising goal from Mário Sérgio. On 14 January 2013, APOEL faced Apollon Limassol at Tsirion Stadium and won by 1–2 with a last-minute winner. Apollon took the lead in the first half, but Selim Benachour's early equaliser in the second half and Hélio Pinto's free-kick winner in the 12th minute of added time secured an important victory for APOEL. On 19 January 2013, APOEL drew 1–1 against eternal rivals Omonia, with Hélio Pinto opening the score early in the first half and Omonia equalising after one hour of play. On 27 January 2013, Gustavo Manduca scored twice in the second half and helped APOEL to beat Olympiakos Nicosia by 0–2 at GSP Stadium. On 2 February 2013, APOEL got a 2–0 home victory against Nea Salamina, in a behind closed doors match. Nektarios Alexandrou opened the scoreline in the first half and Dudu Biton scored on his debut just five minutes after being subbed in the 85th minute. On 11 February 2013, APOEL record its third consecutive 2–0 league win – this time over Ayia Napa at Tasos Markou Stadium – by two goals of Aritz Borda and Dudu Biton. On 27 February 2013, APOEL faced Ethnikos Achna at home in a behind closed doors match and won by 1–0 with an early second half goal from Dudu Biton. On 3 March 2013, APOEL beat AEK Larnaca by 0–1 at GSZ Stadium, with Mikkel Beckmann netting the game's only goal with long-range effort in the 75th minute. So, after 23rd matchweek results, APOEL was only one point behind leaders Anorthosis. On 9 March 2013, Nektarios Alexandrou scored twice to lead APOEL to 2–0 home victory over AEL Limassol and APOEL moved up to first place after four months. On 17 March 2013, APOEL demolished AEP Paphos 6–0 at home, recording seven consecutive wins without conceding a goal and opened up a three-point gap over the second placed team Anorthosis. Mário Sérgio and Mikkel Beckmann scored APOEL's first two goals, while Dudu Biton and Constantinos Charalambides each scored twice for the final 6–0 victory for APOEL. On 31 March 2013, APOEL achieved the most important victory (so far) in the season by beating the second placed team Anorthosis 0–2 at Antonis Papadopoulos Stadium and opened up a six-point gap from its rivals. Dudu Biton gave his team the lead after 68 minutes of play and Nuno Morais secured APOEL's victory 12 minutes later with a long range effort.

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