On 2 September 2019, Barcelona reached an agreement with Las Palmas for the transfer of Pedri, effective as of the following 1 July 2020. The player agreed to a two-year contract with the Catalan club, who paid €5 million for the deal, which would increase as Pedri fulfilled various clauses in his contract. Assigned to the main squad for the 2020–21 season and with the number 16 shirt, Pedri made his debut on 27 September, replacing Philippe Coutinho in a 4–0 home win against Villarreal in La Liga. Pedri received his first start on 17 October in a 0–1 away loss against Getafe. On 20 October, Pedri scored his first goal for the club on his UEFA Champions League debut, in a 5–1 win over Ferencváros in the group stage, after coming on as a substitute in the 61st minute for Ansu Fati. On 7 November, in a 5–2 home win over Real Betis, Pedri scored his first goal in La Liga after an assist from Sergi Roberto.

On 6 January 2021, Pedri scored a headed goal against Athletic Bilbao and assisted Barcelona's second goal in a 3–2 win at San Mamés. On 17 April, Pedri won the first trophy of his senior career after Barcelona beat Athletic 4–0 in the Copa del Rey final. On 8 May, at 18 years and 164 days, Pedri made his 50th appearance for Barcelona in all competitions when Pedri started in the 0–0 draw against Atlético Madrid at Camp Nou, thus becoming the second youngest player to reach this milestone after Bojan Krkić, who was 18 years and 3 days when Pedri reached 50 appearances.

In the middle of October 2021 Pedri signed a new contract with Barcelona which contained a record €1 billion ($1.57 billion) release clause. On 29 November, Pedri won the 2021 Kopa Trophy, which is awarded by France Football to the best performing player under the age of 21. On 13 February 2022, Pedri scored the fastest Derbi barceloní goal of the 21st century, clocking in at 75 seconds in a 2–2 draw against Espanyol.

On April 14 2022, Pedri picked up an hamstring injury during Barcelona's second legged quarter-final UEL clash with Frankfurt, in which they were eliminated. Subsequently, it was announced that Pedri could miss the rest of the season.