Wan-Bissaka was born in England and is of Congolese descent. Wan-Bissaka made a single appearance for DR Congo U20s in an 8–0 friendly loss to the England U17s on 7 October 2015. However, he remained eligible to represent the country of his birth and, after impressing for Crystal Palace, Wan-Bissaka was called up to the England under-20 squad in March 2018. He was sent off during his debut against Poland, although England still won 1–0.

Wan-Bissaka was a member of the Crystal Palace academy from the age of 11, where he started out as a winger. He signed a professional contract with the club in December 2016.

On the 2017 pre-season tour, Wan-Bissaka began to feature with the Palace first team under new manager Frank de Boer, playing in a number of friendlies. The Dutchman played a formation with wing-backs, and this new role emphasised Wan-Bissaka’s defensive capabilities, eventually leading to him moving from a winger to a full-back. However, he saw chances limited in the first half of the season as De Boer showed a preference to play Timothy Fosu-Mensah or Martin Kelly at right-back, then new manager Roy Hodgson favoured Joel Ward. He was an unused substitute a few times under the new manager, while also starring for the Eagles U23 side.

On 25 February 2018, Wan-Bissaka made his first-team debut for Crystal Palace, in the midst of an injury crisis, in a Premier League match against Tottenham Hotspur at Selhurst Park which resulted in a 1–0 defeat. He played all but two minutes of the four Palace matches in March, and won the club’s Player of the Month award with 65% of the supporters’ votes.

On 20 August 2018, Wan-Bissaka was sent off in a 2–0 loss to Liverpool for denying Mohamed Salah a clear goalscoring opportunity. He was named the club’s Player of the Month for August, September, October and March. On 30 April 2019, Wan-Bissaka was named the Crystal Palace Player of the Year for his displays throughout the season.

Wan-Bissaka was called up to the England U21 squad for the first time in September 2018 and made his debut for them on 6 September, playing 90 minutes in a 0–0 draw with the Netherlands at Carrow Road. On 27 May 2019, Wan-Bissaka was included in England’s 23-man squad for the 2019 UEFA European Under-21 Championship. He made one appearance in the tournament, a 2–1 loss against France, in which he scored an own goal.

On 29 June 2019, Wan-Bissaka signed a five-year contract with fellow Premier League club Manchester United. Crystal Palace would receive an initial fee of £45 million, with another £5 million due in potential bonuses. Upon signing for Manchester United, Wan-Bissaka became the sixth-most expensive defender of all time and the most expensive English player who was uncapped by the national side at the time of transfer.

On 11 August 2019, he made his Manchester United debut, playing the full 90 minutes in a 4–0 league victory over Chelsea. On 17 October 2020, as United won 4–1 at Newcastle United, he scored the first goal of his professional career.

In August 2019, Wan-Bissaka received his first call-up to the senior England team, ahead of UEFA Euro 2020 qualifiers against Kosovo and Bulgaria, but was forced to withdraw from the squad due to a back injury.