At 1.93 meters and 88 kg, Sotirios Kyrgiakos is a towering pillar at the back and a man almost impossible to find a way around for many an opponent. The imposing figure from Trikala, Greece previously earned his spurs in Scotland and England before moving to Germany.  The rock-solid centre half is known above all for his aerial superiority – a trait which has also proven fruitful whilst on the attack.

Kyrgiakos made his first football steps with a local team, Thyella Megalochoriou. It did not take long for him to be recognized. At the start of the 1996–97 season he became a member of the Panathinaikos football academy. In the wake of the 1999–2000 season he became a member of Agios Nikolaos. In the 2003–04 season, Kyrgiakos won with Panathinaikos the Greek League and Greek Cup against the eternal rival Olympiakos.

Rangers
The following January, he joined Rangers during the 2004–05 season with a view to a permanent deal. He scored a famous winning goal against F.C. Porto in the UEFA Champions League that year. He left the club by mutual consent in May 2006 after his contract ran out.

Eintracht Frankfurt
In June 2006, Kyrgiakos signed a two-year deal with Eintracht Frankfurt. In his first season, he proved to be a fan favourite with some great performances and crucial goals which helped the team avoid relegation. In his second season with the club with more excellent performances he helped the team finish in ninth position. On 1 July 2008, after his two-year deal expired, Kyrgiakos decided not to renew his contract with the German club, and so was released.

AEK Athens
On 1 August 2008, Kyrgiakos agreed to sign for AEK Athens on a five-year deal. Due to a number of injuries, Kyrgiakos only made 20 league appearances for AEK but he still established himself as one of the league's best defenders. He played in the Greek Cup Final in 2009 as AEK played Olympiakos in one of the most thrilling games in the history of Greek football. Kyrgiakos was on the losing side as Olympiakos F.C. won 15–14 on penalties following a 4–4 draw after extra time. Kyrgiakos did not manage to complete the match though having picked up an injury in the second half of the match. AEK were winning 2–1 at the time.

Liverpool
On 21 August 2009, it was announced that he had signed a two-year deal with the option of a further year for Liverpool. The Greek international was handed the number 16 shirt. Kyrgiakos was voted "Man Of The Match" against Bolton on 30 January 2010 by the Liverpool fans. On 29 July, Kyrgiakos started in Liverpool's UEFA Europa League tie against Rabotnicki Skopje and also featured in both play-off ties against Trabzonspor. On 22 September, he captained the team that lost to League Two side Northampton Town on penalties in the third round of League Cup.

In June 2011, it was announced that Kyrgiakos would get a 12-month contract extension at Anfield after his initial two-year contract expired. After 49 appearances and three goals for the Reds he left the club for Bundesliga side VfL Wolfsburg on 22 August 2011.

VfL Wolfsburg
After discussions with Wolfsburg manager Felix Magath, the Greek stopper was quoted as saying "I am very happy to be joining Wolfsburg. I want to help the VfL finish the season in as high a position as is possible." Magath was hoping that Kyrgiakos made an immediate impact in German football; "Kyrgiakos is a player who will step in straight away to help. He is experienced, knows the Bundesliga and does not need time to adapt. With his commitment, we are able to strengthen defensively." It was later confirmed that he switched on a free transfer after speculation regarding a transfer fee.

Sunderland
On 31 January 2012, Kyrgiakos signed for Sunderland on a loan deal lasting until the end of the 2011–12 season.