[12] Two months later, manager Frank de Boer called him to the senior team for a league match against ADO Den Haag as an injury replacement.

[15] In November 2015, Van de Beek was called to the senior team for a UEFA Europa League match against Scottish club Celtic.

[19] As he scored the goal, his head collided with opposition player Joona Toivio's causing his left eyebrow to bleed.

[26] At the beginning of the 2016–17 season, new manager Peter Bosz included Van de Beek in the Ajax squad for the UEFA Champions League qualification match against Greek club PAOK for a couple of reasons: Bosz was impressed by Van de Beek's performance during pre-season friendlies in Austria, Riechedly Bazoer was injured and Nemanja Gudelj was suspended.

[31] Van de Beek replaced Schöne in the 70th minute of the Europa League final against Manchester United, with Ajax losing the match 2–0.

[32] Commenting on Van de Beek's 2017–18 pre-season matches, the Dutch newspaper Algemeen Dagblad wrote that he had successfully filled the void created by the departure of Davy Klaassen who had recently moved to English club Everton.

In the first leg, he scored an equaliser in the 36th minute of the 1–1 draw; taking an advantage of an error made by opposition goalkeeper Yoan Cardinale.

Van de Beek scored against Juventus on 16 April in the second leg of the quarter-final to help his team knock out the Italian champion with a 3–2 win on aggregate.

[40] On 30 August 2020, Ajax reached an agreement with English Premier League club Manchester United for the transfer of Van de Beek.

[42][43] Van de Beek chose to wear the number 34 jersey as a tribute to former Ajax teammate Abdelhak Nouri, who collapsed during a friendly in 2017 and went into an induced coma.

[44] Van de Beek had little involvement during his first season at Manchester United, starting only four Premier League matches.

Matters did not improve: in the ten Premier League matches under replacement managers Michael Carrick and Ralf Rangnick, Van de Beek totalled only 9 minutes of playing time.

[51] Following his return to Manchester United from his brief loan, Van de Beek continued to have very limited playing time even under former manager, Erik ten Hag, in the 2022–23 season.

[54] On 1 January 2024, Manchester United sent Van de Beek on loan to Bundesliga club Eintracht Frankfurt until the end of the 2023–24 season.

[56] On 11 July 2024, Van de Beek signed for La Liga club Girona after an agreement with Manchester United was reached.

It was disclosed by the Dutch FA that Van de Beek had been battling through injury and as a result, he had trained away from the main squad.

[71] Goal.com described Van de Beek as a player who has "excellent control and a great eye for a pass as he links up with the attack and is dangerous as he makes runs into the box".

[10] Former Ajax captain Joël Veltman described Van de Beek as a player who "works very hard and can play between the lines".