[19] He made his club debut on 26 August against Lecce; he came off the bench in the second half for Matías Vecino, and later helped set-up Antonio Candreva's goal in an eventual 4–0 home win in Inter's opening match of the 2019–20 Serie A season.

[24][25] On 17 January 2021, Barella assisted for the first goal for Arturo Vidal and scored a vital second in a 2–0 home win against rivals and defending champions Juventus in Serie A.

[29] At the end of the 2021–22 season, after having won the Coppa Italia and the Supercoppa Italiana,[30][31] Barella (and his teammate Hakan Çalhanoğlu) totalled 12 assists, which is the highest number for an Inter player since Opta Sports started collecting such data in 2004–05.

[38] He received the Player of the Match award during the tournament for his outstanding performance in the 3-3 draw against Barcelona in the group stage, in which he scored the opening goal.

Barella was called up to the senior Italy squad by manager Gian Piero Ventura for the team's 2018 World Cup qualifiers against Macedonia and Albania in October 2017.

[46] He made his debut for the Italy senior side on 10 October 2018, under manager Roberto Mancini, in a 1–1 friendly draw against Ukraine in Genoa.

[47] On 23 March 2019, Barella scored his first goal for Italy in a 2–0 home win over Finland in a UEFA Euro 2020 qualifying match.

[53] On 10 October 2021, Barella scored the opening goal in a 2–1 home win over Belgium in the bronze medal match of the 2020–21 UEFA Nations League.

[59][60] Italian football journalist Mina Rzouki described him as an intelligent, promising, and composed midfielder, despite his young age, with a wide range of skills.

Barella's performances have also been praised by Italian former footballers Andrea Pirlo and Alessandro Del Piero.

[58] The Italian sports newspaper La Gazzetta dello Sport has compared him to Steven Gerrard, describing him as a dynamic player with good technique, vision, stamina, and physical strength, despite his relatively short stature, as well as an ability to win balls, which enables him to break down possession and subsequently start quick attacking plays.

He is known for his strong character, leadership qualities, competitive spirit, and winning mentality, but has also drawn criticism at times in the press for protesting or arguing excessively with officials during matches.