He made his professional debut in the second round of the Coupe de la Ligue in a 2–1 home loss to Arles-Avignon on 26 August 2014, as a 73rd-minute substitute for Yohann Eudeline.

[19] During the entirety of the 2017–18 Ligue 1 season, he was a regular in a Lille side that narrowly avoided relegation, missing only two games and scoring 13 times, including two apiece in away wins at Metz and Toulouse.

[29] He scored his first European goals in Arsenal's UEFA Europa League 3–2 home win over Vitória de Guimarães on 24 October, two free-kicks.

[30] On 1 January 2020, Pépé scored Arsenal's first goal in a 2–0 home victory over Manchester United, marking new head-coach Mikel Arteta's first win.

[32] On 28 June, he scored his first FA Cup goal in a 2–1 away win against Sheffield United in the quarter-finals, giving Arsenal the lead in the 25th minute from the penalty spot.

[33] On 1 August, he played the whole 90 minutes of the FA Cup Final match against Chelsea to win his first club trophy as an Arsenal player, contributing the assist for Aubameyang's second goal.

[34] On 22 November 2020, Pépé received the first red card of his career in a 0–0 away draw against Leeds United after clashing heads with Ezgjan Alioski in the 51st minute.

[42] He made his debut three days later in a friendly of the same score against his birth nation, France, at the Stade Bollaert-Delelis in Lens, playing the final four minutes in place of Max-Alain Gradel.

[43] Pépé was named in Michel Dussuyer's 23-man squad for the 2017 Africa Cup of Nations in Gabon, but took no part as the Elephants were eliminated in the group stage.

[19][49] Pépé was involved in the Amazon Original sports docuseries All or Nothing: Arsenal, which documented the club by spending time with the coaching staff and players behind the scenes both on and off the field throughout their 2021–22 season.