N’Gog started his career with Paris Saint-Germain of Ligue 1 in 2001. He signed his first professional contract in June 2006.

N’Gog has played for France at many youth levels. He scored one goal in a 2–0 victory over England under-19s in 2007.

Manager Rafael Benítez hailed his scouting network after his signing, saying that “They are finding players like N’Gog, players with quality who are not a high price”. N’Gog played his first game for Liverpool in a friendly game against Villarreal on 30 July 2008 and scored his first goal one game later against Rangers in another pre-season friendly. He then followed this up by scoring Liverpool’s final goal in their next pre-season friendly, a 4–1 win over Norwegian side Vålerenga. He made his Premier League debut against Aston Villa, coming on as a substitute for Fernando Torres. N’Gog scored his first goal for Liverpool in their 3–1 victory over PSV Eindhoven in the group stages of the UEFA Champions League. N’Gog made his first start for Liverpool on 7 February 2009 against Portsmouth, and scored his first league goal on 3 March 2009 against Sunderland in a 2–0 win at Anfield. N’Gog scored his second league goal for the club on 11 April 2009 against Blackburn Rovers at Anfield in an emphatic 4–0 win.

In November 2009, David N’Gog was approached to play for Cameroon, despite having already represented France at youth levels. The then Liverpool striker said: “I have had contact with the Cameroonian federation. Now I need some time to think about things. I’m very flattered.” In February 2010, with Cameroon preparing for the 2010 World Cup, Cameroon’s Minister of Sports, Michel Zoah, met with N’Gog’s father on two occasions to try and convince the player to switch allegiances. A few months later, in May, N’Gog was not included in Cameroon’s preliminary squad for the World Cup. When asked why, Cameroon coach Paul Le Guen said that N’Gog had insisted on a starting spot with the Indomitable Lions. However, N’Gog refuted the claims.

On 31 August 2011, for £4 million transfer fee, Liverpool announced that N’Gog had completed a move to Bolton Wanderers in a three-year deal. N’Gog made his first appearance for Bolton as a substitute for Kevin Davies in Bolton’s 5–0 defeat to Manchester United at the Reebok Stadium on 10 September. His first goal for Bolton Wanderers came in Bolton’s 3–1 win against Wigan Athletic at the DW Stadium on 15 October. Fulham made an unsuccessful £3 million bid for him in August 2012.

On 27 January 2014, N’Gog joined Premier League side Swansea City until the end of the season, signing for an undisclosed fee. He made his debut for the club on 1 February 2014 as a substitute for Nathan Dyer in a 2–0 away defeat to West Ham United.

On 1 September 2014, N’Gog ended his six-year spell in the English leagues after signing a two-year contract with Ligue 1 outfit Reims.

On 12 August 2016, Superleague Greece club Panionios announced that they had signed N’Gog for an undisclosed fee.

On 23 January 2018, N’Gog joined Ross County of the Scottish Premiership on a deal until the end of the 2017–18 season. The Frenchman reunited with Owen Coyle, who had managed him at Bolton Wanderers. He scored his first goal for the club in a 2–1 loss to Rangers on 28 January 2018.

In August 2018, N’Gog joined Hungarian club Budapest Honvéd. On 25 August, he scored seven minutes into his debut against Debrecen.

In February 2020 N’Gog became a member of Lithuanian A League side FK Žalgiris.

On 21 June 2020, Žalgiris announced that N’Gog had officially retired from professional football at the age of 31.