As an academy graduate of River Plate, Fernández made his first-team debut for the club in 2019, before spending two seasons on loan with Defensa y Justicia.

Born in San Martín, Buenos Aires, to Raúl and Marta; Fernández has four brothers, Seba, Rodri, Maxi and Gonza.

[5] He was introduced to football at a young age, playing for a local side called Club La Recova, before joining River Plate.

[7] He progressed through the youth ranks, and was promoted into the club's first-team by manager Marcelo Gallardo on 27 January 2019, in a 3–1 home loss to Patronato in the Primera División, despite remaining on the bench.

[11] Following a promising start in the 2022 season, which he scored eight goals and provided six assists in 19 games, Fernández was named the best active footballer in Argentina, being subsequently scouted by a number of established European teams.

[15][16] Following River Plate's round of 16 exit from the Copa Libertadores, on 14 July, Benfica confirmed the deal,[17] giving Fernández the number 13 shirt, previously worn by club legend Eusébio.

[21] Following Fernández's success internationally at the 2022 FIFA World Cup, he was linked with a move to Premier League teams Chelsea and Liverpool[22] in the January 2023 transfer window, however Benfica were adamant he wouldn't be sold for less than his €121m release clause.

[5][32] On 3 November 2021, he was called up by Argentina national team manager Lionel Scaloni for two 2022 FIFA World Cup qualifiers against Brazil and Uruguay.

[34] After coming on for Guido Rodríguez in the 57th minute, on 26 November, Fernández scored his first international goal, closing Argentina's 2–0 group stage win against Mexico.

[35] In doing so, he became the second youngest player ever (only behind Lionel Messi) to score a World Cup goal for Argentina at 21 years, ten months and thirteen days old.

[37] After defeating Croatia 3–0 in the semi-final, Fernández played in the final against France, where Argentina won the World Cup by a score of 4–2 on penalties after a 3–3 draw.

[41] In July 2024, following Argentina's Copa América triumph, a video showing Fernández and other Argentinian players chanting alleged racist chants about the origin of France national team players on the team bus surfaced, which led to outrage and criticism from the French Football Federation (FFF) and French sports minister Amélie Oudéa-Castéra.

Although he prefers operating centrally, he can be seen occupying the left half-space assisted by a defensive midfield partner, like his former Benfica team-mate, Florentino Luís.

[49][50][51][52] Fernández is named after three-time Copa América winner and former River Plate player Enzo Francescoli, due to his father Raúl's fascination with the Uruguayan.

[53] On 31 October 2024, Cervantes announced on her Instagram story that she and Fernandez were separating, writing (translated from Spanish) "Enzo and I have decided to take some distance from each other today.