[18] On 26 January 2006, De Jong signed a four-and-a-half-year contract at Bundesliga club Hamburg, the transfer fee approximately €1 million.

[24] On 21 January 2009, De Jong was signed to Manchester City for an estimated fee of £18 million[5] by manager Mark Hughes who deployed him in the role of midfield enforcer in a team whose defence badly needed reinforcement.

[28] By the end of the season he had become a firm fans' favourite as well as being one of new manager Roberto Mancini's first picks as defensive midfielder as the team narrowly missed out on a Champions League berth.

[30] De Jong was a member of the City side which won the 2010–11 FA Cup and the 2011–12 Premier League, making 137 appearances and scoring twice before being sold to A.C. Milan in August 2012.

[37] On 31 January 2016, it was reported that De Jong had negotiated to terminate his contract with Milan and joined LA Galaxy on a free transfer, signing a one-year deal.

[38] He was involved in a controversial incident in a game against the Portland Timbers on 10 April when his strong tackle left Darlington Nagbe injured and in need of treatment.

[39] He received a red-card after a bad tackle on Blas Perez on 5 July; although a man down, the Galaxy were still able to hold on for the win over Vancouver Whitecaps FC.

[40] On 29 August 2016, the Galaxy announced that they and the Dutch midfielder mutually agreed to terminate de Jong's contract, freeing the 31-year-old to sign with Turkey's Galatasaray.

In the early stages of the match, De Jong made a chest high challenge on Xabi Alonso, with his studs making contact with the Spaniard's ribs.

However, a groin injury led to his substitution in the 9th minute of the Round of 16 match win over Mexico and it was later confirmed the De Jong would be unable to take any further part in the tournament.

Described as a "tireless grafter" by The Telegraph,[58] his work-rate and tenacity,[59] combined with his new approach to midfield play, earned him the nicknames "der Rasenmäher" ("the Lawnmower"),[12] "The Terrier,"[60] and "The Destroyer.

[62] Sometimes De Jong is the sole holding midfielder, but often he plays alongside another defensive player, such as Gareth Barry at Manchester City or Mark van Bommel for the Dutch national team.

[63] In addition to his defensive capabilities and ability to cover ground, De Jong was also a competent passer;[64] he had the highest passing completion percentage in the Premier League in the 2010–11 season out of the top 50 players (90%).

[65] Despite his ability, and reputation as one of the best defensive midfielders in the world at his peak, De Jong has also drawn criticism over his feisty, physical, and combative playing style, including from his former Dutch national team manager Van Marwijk.

[67] In the 2010 FIFA World Cup Final he kicked Spanish player Xabi Alonso in the chest, a challenge for which De Jong admitted he was lucky not to have received a red card.

[68] On 3 October 2010, in a Premier League match against Newcastle United, a tackle by De Jong on Hatem Ben Arfa resulted in the latter being carried off the pitch with a double fracture of his left tibia and fibula.

[60] Indeed, despite his reputation as an aggressive and hard-tackling player,[71][72] De Jong's first official direct card of his career came with Milan, in a 1–1 away draw against Verona in Serie A on 13 December 2015;[73][74] previously, he had only been sent off once in an official game, namely for two bookable offences in a match for Hamburg against Rapid Bucharest in the 2005–06 edition of the UEFA Cup, while his only direct red card had come against Werder Bremen, in the semi-finals of the 2006 DFL-Ligapokal.

[22][71][75] In April 2016 while playing for the LA Galaxy De Jong was involved in another controversial incident when a strong takedown led to Portland Timbers midfielder Darlington Nagbe being removed from the field with an injury.

The tackle led to a 3-game suspension for De Jong after the disciplinary committee determined the action to have been, "a clear and unequivocal red card.