Kompany made his international debut aged just 17 for Belgium in February 2004 against France, as one of the youngest players ever.

On 9 June 2006, however, it was announced that Kompany had been acquired by Hamburger SV for a fee of €10 million, as a replacement for fellow Belgian Daniel Van Buyten. In his debut season for Hamburg, he managed only six Bundesliga starts for the club before suffering an achilles injury in November that ruled him out for the rest of the season. Despite his lack of involvement in the season, he was selected in a 30-man provisional squad for the 2007 UEFA European Under-21 Football Championship.

On 22 August 2008, Premier League club Manchester City signed Kompany from Hamburg on a four-year contract for an undisclosed fee. Two days later, Kompany made his Manchester City debut against West Ham United. On 28 September, Kompany scored his first goal in City’s 2–1 away defeat by Wigan Athletic. On 28 December 2008, he started the game with Blackburn Rovers at Ewood Park, completing the full 90 minutes in a 2–2 draw. During his early time at Manchester City, Kompany played as a defensive midfielder.

On 19 October 2009, Kompany signed a new five-year deal with City that would keep him at the club until 2014. He scored his second league goal for the club in a 2–0 home win against Portsmouth and his third in a 6–1 away win against Burnley at Turf Moor.

In November 2009, Kompany fell out with the Belgium manager Dick Advocaat. On the Monday before the friendly match with Qatar on 18 November 2009, Kompany received permission to attend the funeral of his grandmother as long as he returned to the team hotel before 6 pm that evening. As it happened, he did not return until nearly midnight. Furious, Advocaat removed him from the squad altogether, although on 24 February 2010 he was recalled to the Belgium squad by Advocaat for the friendly against Croatia.

Kompany was handed the number 4 jersey for the 2010–11 season after previous wearer Nedum Onuoha moved on loan to Sunderland. On 14 August 2010, he started the opening Premier League fixture and received a yellow card from referee Andre Marriner against Tottenham Hotspur at White Hart Lane and completed the full 90 minutes alongside Kolo Touré in a 0–0 draw. Kompany put in a man of the match performance in the 1–0 home win against Chelsea at the City of Manchester Stadium on 25 September. On 10 November, Kompany started the Manchester derby league game with Manchester United at the City of Manchester Stadium and played the full 90 minutes in a goalless draw.

On 19 May 2010, Kompany scored a 90th-minute goal to give Belgium a 2–1 win over Bulgaria in a friendly. On 10 November 2011, a day before the friendly against Romania, Georges Leekens named Kompany as Belgium captain, succeeding Thomas Vermaelen.

On 12 February 2011, he started the League match against Manchester United at Old Trafford and played the full 90 minutes, partnering with Joleon Lescott in a 2–1 defeat. On 25 April, he again continued to captain the side in the absence of striker Carlos Tevez against Blackburn Rovers at Ewood Park, playing the full 90 minutes alongside Lescott in an important 1–0 victory courtesy of a late 75th-minute strike from Edin Džeko. On 16 April, Kompany captained Manchester City’s victory over main rivals Manchester United in the FA Cup semi-final at Wembley Stadium; City won the game 1–0. Later that day, he was named in the PFA Team of the Year alongside teammate Tevez.

In the 2011 FA Cup Final he started and finished the match, a 1–0 victory over Stoke City which delivered Manchester City’s first major trophy for 35 years. At the end of the 2010–11 season, in which City qualified for the UEFA Champions League for the first time, manager Roberto Mancini praised Kompany’s “incredible” season and claimed that with his attitude and mentality, Kompany can become one of the best defenders in Europe.

Kompany was firmly installed as club captain for the 2011–12 season, with Tevez having expressed publicly his desire to leave the club. The opening fixture on 7 August 2011 was the Community Shield, which ended in a 3–2 defeat to rivals Manchester United despite City holding a two-goal lead at half-time.

Kompany married his Mancunian girlfriend, Carla Higgs, a lifelong Manchester City supporter on 11 June 2011, and together they have a daughter, Sienna, who was born on 10 June 2010, and two sons, born in 2013 and 2015.

On 30 April 2012, Kompany scored a header from a David Silva corner in the Manchester derby; the game finished 1–0 to City and put them in first place ahead of Manchester United on goal difference with only two games of the season remaining. On 13 May, the final day of the Premier League season, Kompany led the team against Queens Park Rangers which ended in a dramatic 3–2 win, securing the league title for the club for the first time since 1968. QPR midfielder Joey Barton attempted to headbutt Kompany during the match. On 25 July, Kompany signed a six-year contract with Manchester City, the longest of its kind in the club’s history.

After 34 minutes of Belgium’s 2–1 World Cup qualifier win against Serbia in June 2013, Kompany suffered concussion and facial injuries, including a broken nose and cracked eye-socket, in a collision with goalkeeper Vladimir Stojković. After receiving first aid on the touchline, he played out the remainder of the match.

In March 2013, Kompany bought the Belgian third division club FC Bleid as a “social commitment towards the youngsters of Brussels”, with the intention of offering disadvantaged youngsters the opportunity to use sport as a vehicle for self-improvement.

On 2 March 2014, Kompany captained the Manchester City team that won the League Cup Final, beating Sunderland 3–1. On 11 May, he scored Manchester City’s second goal in a 2–0 win against West Ham United as the club won the 2013–14 Premier League title.

On 13 May 2014, Kompany was named in the Belgium squad for the 2014 FIFA World Cup. He captained the Red Devils in their first World Cup match in 12 years, a 2–1 win against Algeria in Belo Horizonte.

In April 2014, Kompany opened two new sports bars in Belgium by the name of Good Kompany, one at the Grand Place in Brussels and the other at the Groenplaats in Antwerp. However, Kompany closed down both bars within a year of their opening. At the time of their closure, Kompany was quoted as saying “I regret this decision. We had enough customers, turnover was good, but not enough to cover the costs. So that’s where it ends. Lesson 1 in business: investments are always a risk. You win some, you lose some.”

During 2014–15, Kompany accumulated 33 appearances in all competitions, but the club could only finish runners-up in the league and were eliminated from the domestic and continental cups at early stages, also losing out in the Community Shield. In April 2015, he suffered a muscular injury during the Manchester derby which ended his campaign early, and this would prove to be the start of a long spell of recurring injuries (mainly muscular strains) for a player who had already endured a number of physical problems since his arrival in England.

After scoring in the team’s opening two Premier League fixtures, Kompany suffered a strain to his calf in the opening weeks of the 2015–16 season and lasted just minutes into his comeback match in December. in February 2016, he was fit to take part in the League Cup Final in which City defeated Liverpool, and was named man of the match; however in May he was again forced off in the early stages of the Champions League semi-final, finishing on 22 appearances and subsequently missing Euro 2016 with Belgium.

Having returned to the first team in October 2016, on 9 November Kompany withdrew from international duty with discomfort, and on 22 November he sustained a knee injury. At that time, an analysis showed that he had suffered 37 injuries since joining Manchester City in 2008 and had missed over two years (878 days) in that eight-year period. By April 2017 he had recovered, and scored in a victory over Tottenham Hotspur, commenting on his issues that “The main thing is self-belief and experience”. Manager Pep Guardiola kept Kompany in the team for the FA Cup semi-final, and he played the entirety of the match which went to extra time; City lost the tie to eventual winners Arsenal, finishing 2016–17 without a trophy. Kompany appeared just 15 times during the campaign, although his continued importance to the team was evidenced by the fact he would always return to the starting line-up as soon as he was fit.

Kompany played in eight league matches for Manchester City during the first portion of 2017–18, suffering further strains during the period, before withdrawing minutes into an away fixture against Newcastle on 27 December; Guardiola’s responses in the press conferences suggested he was losing patience with the situation. He returned to the team on 3 February 2018, completing the 90 minutes of a 1–1 draw away to Burnley while Aymeric Laporte, the club’s new record signing in the same position, remained on the bench throughout. On 25 February, he scored Manchester City’s second goal of a 3–0 victory over Arsenal in the 2018 EFL Cup Final, and was named man of the match. he eventually managed 17 league starts as Manchester City won the title with a record 100 points.

At the 2018 FIFA World Cup in Russia, Kompany featured in five of his nation’s seven matches, playing every minute in the knockout phase as they advanced to the semi-finals before losing to eventual champions France, overcoming England to finish third, their highest ever placing in the competition.

Kompany’s father, Pierre, is a Congolese immigrant to Belgium and serves as his agent. In October 2018, Pierre was elected the mayor of Ganshoren, making him the first black mayor in Belgium. His late mother, Jocelyne, was Belgian. His brother, François Kompany, plays for Roeselare, having previously had spells at Germinal Beerschot and Macclesfield Town. Kompany also has an older sister. Among his friends are former Chelsea goalkeeper Yves Ma-Kalambay and former Manchester United defender Floribert N’Galula, both of whom he consulted about his move to England before joining Manchester City.

Kompany has a number of pastimes and interests which keep him occupied outside of football. He has an interest in politics and graduated with an MBA at Manchester Business School in 2018 after several years of study. Kompany has been characterized as “erudite” and “eloquent”.

On 6 May 2019, Kompany scored Manchester City’s only goal during a 1–0 victory over Leicester City with his first goal from outside the box for the club. The result put the club one point ahead at the top of the 2018–19 Premier League table, and they retained the title by the same margin six days later. Kompany had already lifted the EFL Cup again in February 2019 after a penalty shootout victory over Chelsea. He played the whole of the 2019 FA Cup Final, a 6–0 victory over Watford as the club completed an unprecedented domestic treble (plus the Community Shield).

On 19 May 2019, it was announced that Kompany would be leaving Manchester City to become player-manager of Anderlecht. With two defeats, two goalless draws, six goals conceded and three scored, the Brussels-based club had endured their worst opening start to a league campaign since the 1998–99 season. On 22 August 2019, Kompany decided to step down managerial duties on the pitch, to focus primarily on being a player. Head coach Simon Davies would become in charge of tactical changes and substitutions, while Kompany would be given the captain’s arm band.

On 17 August 2020, it was announced that he would be the head coach at Anderlecht for the next four seasons, after retiring from professional football on the same day.