Born in France, he could have elected to play for France internationally, but chose instead to play for the national side of his ancestral country, Mali.
Sissoko played as a second striker in the youth system of French club AJ Auxerre.
In 2003 Sissoko made a free transfer to Spanish club Valencia CF, managed by Rafael Benítez, where he was deployed in midfield. Valencia won the 2003–04 La Liga title and in the same year became UEFA Cup champions, during which Sissoko played nine matches. The following year, Benítez left to manage Liverpool and was replaced by Claudio Ranieri.
Sissoko moved from Valencia to Liverpool for £5.6 million in the summer of 2005. His first appearance was against Kaunas on 26 July 2005 in the UEFA Champions League qualifiers. In February 2006, he suffered serious eye injury after collision with Benfica's midfielder Beto.
Sissoko was part of the FA Cup winning side in 2006 and played an integral role for the team. In the summer of 2007, Sissoko rejected offers from Barcelona, CSKA Moscow and Juventus to stay on Merseyside. His only goal for Liverpool came on 25 August 2007, a low shot from twenty yards out against Sunderland in a 2-0 away win.
In January 2008 Sissoko transferred to Italian club Juventus, where he would team up with former coach Claudio Ranieri, for a fee of €11 million. He made his first appearance for the club in February 2008, coming in as a 67th minute substitution for Tiago in a Serie A fixture versus Cagliari Calcio. Sissoko scored his first goal for Juventus on 2 March 2008, the equaliser against Fiorentina. During the first half of the 2008–09 season, he regularly featured in the starting line-up, forming a partnership with youngster Claudio Marchisio as the centre midfield pair in Claudio Ranieri's 4–4–2 formation. His season ended early after he broke his foot in March 2009 ruling him out for the rest of that season and into the start of the 2009-10 season.
Sissoko's injury problems continued throughout the rest of the 2009-10 season and into 2010–11 season, as he suffered thigh strains, a leg strain, Achilles tendon inflammation, and finally season-ending knee surgery in March 2011.
On 28 July 2011, Sissoko moved to Ligue 1 side, Paris Saint-Germain for a transfer fee of €7 million + €1 million should Paris Saint-Germain qualify for the Group Stage of the UEFA Champions League before September 2013. Sissoko scored his first goal for PSG in November, when he headed in a cross from Nenê, in a 1–1 draw against Bordeaux at the Stade Chaban Delmas. In April 2012 Sissoko captained the squad against rivals Olympique de Marseille in Le Classique, but was sent off in the 86th minute for two bookable offences in a game that finished 2–1 to the Parisian club. On 30 January 2013 Sissoko joined Fiorentina on loan. On 3 September 2013 Sissoko left Paris Saint-Germain by mutual consent.
On 30 January 2014, Sissoko joined the La Liga side Levante on a six-month deal after spending nearly five months without a club.
On 25 June 2015, Sissoko transferred to Chinese Super League side Shanghai Shenhua. On 21 February 2016, Sissoko was released by Shanghai Shenhua.
On 1 October 2016, Sissoko joined Indian Super League side FC Pune City as a marquee player.
On 17 February 2017, Sissoko joined Ternana Calcio on a six-month contract. On 12 March 2017 he terminated his contract with Ternana after 25 days with the club.
On 13 April 2017, Sissoko joined Indonesian club side Mitra Kukar on a one-year contract.
Born in Mont-Saint-Aignan, France, Sissoko was eligible to play for the French national football team but opted to play international football for his ancestral country, Mali. Sissoko obtained his first international call-up in 2004, and has appeared for his country in almost all African Cup of Nations qualifiers and tournaments since then. He has also featured in FIFA World Cup qualifiers for both 2006 and 2010. Sissoko has made 34 official appearances for Mali, and has scored 2 goals. With the Mali national football team, he finished fourth in the 2004 African Cup of Nations, and third in the 2013 African Cup of Nations.
A large, quick, combative, and physically strong central defensive midfielder, Sissoko excels as a ball winner, a role which allows him to support his more offensive midfield teammates defensively by laying off the ball to them after winning back possession. Due to his tenacious tackling, stamina, work-rate, and tacitcal intelligence, he has been compared to former French midfielder Patrick Vieira, also earning the nickname "La Piovra" (the octopus) during his time with Juventus, due to his long limbs and energetic style of play. In addition to his ball-winning abilities, and his physical and athletic attributes, he is also known for his powerful striking ability from distance.
Sissoko is the nephew of former African Footballer of the Year Salif Keïta, who, like Sissoko, played for Mali and Valencia CF. Salif Keita is also the uncle of former FC Barcelona midfielder Seydou Keita. Both Sissoko and Seydou Keita play similar roles as hard-tackling central defensive midfielders. Sissoko is sometimes referred to as "the Black Ninja" for his tenacious tackling and work rate. He has no relation to football player Moussa Sissoko, but is the elder brother of Abdou Sissoko.
Sissoko has said "I am proud of being a Muslim and I follow Ramadan even during the football tournament," on the Dubai-based Arab TV network, Al Arabiya.As of 28 July 2017
La Liga: 2003–04
UEFA Cup: 2003–04
UEFA Super Cup: 2004
FA Cup: 2005–06
FA Community Shield: 2006
UEFA Super Cup: 2005
Ligue 1: 2012–13