[4] He also made the substitutes bench in the UEFA Champions League against Real Madrid and Lazio, and featured in several Greek Cup games.

[6] On 1 December, in a group stage game in the Europa League, Papadopoulos scored the opening goal in a 2–1 win over Steaua București.

Since joining Schalke from Olympiacos, Papadopoulos has played in over 70 matches in all competitions, scoring five goals and has ultimately gathered respect and praise from all over Europe due to his tenacious and skillful defending considering his young age.

A virus, however, would later kept him out of play for a number of games, and he would later undergo surgery in an attempt to correct a knee injury he suffered in a 3–1 loss away at Hamburger SV in November 2012.

After a very difficult year for the defender marred by injury (383 days to be exact), Papadopoulos returned to action in a home game against SC Freiburg in December 2013.

The centre-back suffered the injury in the final training session ahead of his side's UEFA Champions League away match with Zenit Saint Petersburg; he underwent surgery.

[20][21] On 7 June 2015, Bayer Leverkusen opted to make Papadopoulos' loan from Schalke 04 permanent on a €6.5 million transfer fee, with the player signing a five-year contract.

[26] On 13 January 2017, after a frustrating first half of the campaign with RB Leipzig and due to their acquisition of defender Dayot Upamecano from Salzburg during the winter transfer window, Papadopoulos moved to Hamburger SV.

On 3 February 2017, Papadopoulos scored a headed goal from a set piece against Bayer Leverkusen, giving Hamburg a 1–0 victory over his parent club.

[35] On 27 October 2020, the Croatian football club based in Zagreb Lokomotiva officially announced the signing of Greek international for an undisclosed fee.

[36][37] On 18 July 2021, he moved to Saudi Professional League side Al-Fayha, on a free transfer from NK Lokomotiva, for a two-years' contract for an undisclosed fee, increasing the parish of the Greeks in the club after the signing of Panagiotis Tachtsidis.

[38] On 28 August 2021, Kyriakos Papadopoulos is looking for the next club of his career, as he is solved his contract with Al-Fayha, after a month of his presence in Saudi Arabia.

[39] On 9 September 2021, Papadopoulos returned to Super League Greece, by signing a season-long contract with Atromitos for an undisclosed fee.

[42] On 15 February 2023, Papadopoulos returned to Super League Greece, by signing a season-long contract with Lamia for an undisclosed fee.

He appeared in all three group games against Moldova, Netherlands and Russia, helping Greece finish top and qualify for the finals.

[45] He finished an excellent season with Schalke when, on 4 June 2011, the then-Greece head coach, Fernando Santos, called up Papadopoulos for a rookie spot on the team for a match against Malta.

Due to an injured Avraam Papadopoulos and Sokratis Papastathopoulos being unable play, he took their place in the squad in the centre of defence next to Vangelis Moras.

On 17 April 2015, Papadopoulos was recalled by new Greece manager Sergio Markarián, as part of a selection overhaul, to participate in the nation's European Championship qualifier away at Hungary.