A product of Sporting CP, João Mário won the Portuguese cup there before moving to Inter Milan in 2016, with subsequent loan spells at West Ham United, Lokomotiv Moscow and back at Sporting. He joined Benfica permanently in July 2021.

An attacking midfielder who can also play wide, he is known for late runs into the box, set-piece delivery and shooting from distance, and he was central to Benfica's league title in 2022/23.

He played no part in Benfica's 2024/25 campaign, joining Beşiktaş on loan in September 2024. The move contained an obligation to buy that was triggered the following June, ending his time at the club.

He won UEFA Euro 2016 with Portugal and retired from international football in 2023 with more than eighty caps.