Memphis began his professional career with PSV Eindhoven, where, under the influence of manager Phillip Cocu, he became an integral part of the team, scoring 49 goals in 124 games across all competitions.

He made his official debut on 21 September 2011 in a KNVB Cup second round match against amateur side VVSB, opening an 8–0 away win.

[11] His first Eredivisie match was 26 February 2012, when PSV beat rivals Feyenoord 3–2[citation needed] at the Philips Stadion, coming on in added time for Zakaria Labyad.

[13] On 5 August, Memphis featured in the 2012 Johan Cruyff Shield at the Amsterdam Arena, replacing Luciano Narsingh for the final six minutes as PSV defeated league champions Ajax 4–2.

[17] Memphis provided the assist for Tim Matavž's goal against Roda JC on 27 October, but picked up two second-half yellow cards and was sent off for the first time in his professional career as PSV lost 2–1.

[21] After a successful showing at the 2014 World Cup, Memphis was linked to a number of clubs, including Chelsea, Manchester United[22] and Tottenham Hotspur.

[24] In the opening game of the Eredivisie season three days later, Memphis played a major part in PSV's 3–1 away win against promoted side Willem II by scoring two goals.

[25] He improved on this performance in the following game, scoring two free-kicks and delivering the assist for Georginio Wijnaldum's goal in a 6–1 home win against Breda.

[26] On 28 August, in the Europa League play-off second leg away in Belarus, he scored two late goals against Shakhtyor Soligorsk as PSV won 3–0 on aggregate to reach the group stage.

[36] On 12 June, United confirmed the signing of Memphis, for a reported fee of £25 million on a four-year contract with the option to extend for a further year.

[39] This made him the fourth player to join United from PSV after Jaap Stam, Park Ji-sung and Ruud van Nistelrooy.

Memphis made his debut in a pre-season friendly against Club América in Seattle on 17 July, contesting the first half as United fielded a different 11 players for each 45 minutes.

[41] At his own request, after the departure of Ángel Di María, Memphis was given the iconic number 7 shirt – previously worn by former players such as George Best, Bryan Robson, Eric Cantona, David Beckham and Cristiano Ronaldo.

[47][48] Following his early struggles in the Premier League, Memphis told Dutch newspaper De Telegraaf, "There are a lot of games in Manchester.

These claims were dismissed by assistant manager and former United player Ryan Giggs, who blamed Memphis' flashy lifestyle for his poor form.

[49][better source needed] Memphis was later dropped to the bench, along with countryman Daley Blind, during United's 3–0 win over Everton on 17 October, following the Netherlands' failure to qualify for UEFA Euro 2016.

After being dropped in four consecutive matches, Memphis got his first start as a second striker due to Anthony Martial and Rooney's unavailability, and seized the opportunity with his second league goal in a 2–1 away win over Watford at Vicarage Road.

[65] On 15 December, Memphis tore his anterior cruciate ligament while playing against Rennes in Ligue 1, ending a successful season during which he had scored nine goals in 12 league starts for Lyon.

[66] He returned from his injury to start for Lyon in their 5–6 penalty shootout loss in the French league cup final against Paris Saint-Germain on 31 July 2020.

[67] On 7 August, Memphis scored in his sixth consecutive Champions League match, converting a penalty in a 2–1 loss to Juventus in the second leg of their round of 16 tie; he is only the second Dutch player to score in six straight Champions League games, following former Manchester United striker Ruud van Nistelrooy.

Memphis made his international debut on 15 October 2013, coming on for Jeremain Lens in the last minute of a 2–0 away win against Turkey at the Şükrü Saracoğlu Stadium in World Cup qualification.

[88] Memphis was selected by Netherlands manager Louis van Gaal in the final 23-man squad for the 2014 FIFA World Cup in Brazil.

[89] He came on as a substitute before the half-time whistle in the second group match against Australia to replace defender Bruno Martins Indi, who had sustained a head injury, and in the 68th minute he scored the winning goal, a swerving effort from outside the box.

[91] He came on as a substitute again in the final group match against Chile on 23 June in São Paulo and scored the second goal for the Dutch, tapping in an Arjen Robben cross, as they clinched first place with a 2–0 victory.

[94] Memphis' first goal since the World Cup came in a friendly at the Amsterdam Arena on 5 June 2015, deflecting Klaas-Jan Huntelaar's shot to put the Netherlands 3–1 up against the United States, although the team eventually lost 4–3.

[98] On 7 September 2021, Memphis scored his first international hat-trick in a 2022 World Cup qualification 6–1 win over Turkey, reaching 33 goals and equaling Johan Cruyff's and Abe Lenstra's goalscoring tallies for the Netherlands.

[99] Memphis scored a last-minute winner against Wales on 14 June 2022 in the UEFA Nations League, taking him to 42 international goals, level with Klaas-Jan Huntelaar.

[123] This followed two more releases so far in 2023 including "Asem Beba"[124] in February and "Leven Als Een Prof",[125] translating to 'life as a professional', in April.

In October 2023, Memphis released "Baby Don't Play", an all English afro-beat track in a style which is inspired by his Ghanaian roots.

[136] In April 2020, Memphis was criticised by several animal rights organisations for posting pictures of himself with a liger cub while on vacation in Dubai.