Playing in the youth academies of De Graafschap and Ajax, he made his professional debut for the Amsterdam-based side and would go on to become the club's captain as they won a club-record four consecutive Eredivisie titles from 2011 to 2014.

He grew up in Doetinchem and graduated from the same school (het Rietveld Lyceum) as Guus Hiddink, Paul Bosvelt and Klaas-Jan Huntelaar, which grants him immediate university access (he has considered studying economics).

On 21 February, he scored a brace against Vitesse in a 4–0 win to keep Ajax's push for UEFA Champions League qualification alive.

On 15 May 2011, De Jong played in the title-decider game against Twente and helped Ajax win its first—and 30th overall—Eredivisie title since 2004 by scoring two goals, sealing the 3–1 victory.

On 11 April 2012, he scored a hat-trick as Ajax defeated ten-man Heerenveen 5−0 in the 29th league game of the season and moved three points clear of second-placed AZ in the Eredivisie table.

[15] On 1 July 2014, De Jong signed a six-year deal with Newcastle United for a fee believed to be around £6 million.

[19] Upon his return to the team, De Jong scored his first Newcastle goal in a 3–2 loss against Swansea City on 25 April 2015.

In January 2016, De Jong was sidelined for two weeks in a freak accident in which one of his contact lenses was pushed into his eye, threatening his sight.

Asked about his longer-term future, De Jong said that it would be ideal if Newcastle "are promoted first and then I return to play in the Premier League", which eventually proved successful on 25 April 2017 after beating Preston 4–1.

[22] On 28 August 2017, it was announced that de Jong would return to Ajax, signing a three-year contract with the Amsterdam club.

[23] On 23 August 2018, de Jong joined A-League side Sydney FC on a season-long loan deal.

[33] On 11 August 2010, De Jong made his debut for the senior side in its 1–1 draw with Ukraine in a friendly match, playing the first 62 minutes.

[35] He scored his first two goals for the Netherlands under Louis van Gaal in a friendly encounter against Indonesia at the Gelora Bung Karno Stadium, Jakarta on 7 June 2013.