Enzo Jeremías Fernández was born in San Martín, in Buenos Aires Province, and was formed at CA River Plate, whom he joined as a child. After a productive loan at Defensa y Justicia in 2020/21 he returned to River and became a first-choice midfielder, winning the Primera División title in 2021.

Benfica signed him on 14 July 2022 for a reported €10 million plus add-ons. He adapted immediately, taking a starting role in Roger Schmidt's midfield and scoring in the Champions League play-off against Dínamo Kiev and in the group stage. His form earned a call-up to Argentina's World Cup squad, where he started the majority of the matches, scored against Mexico and was named the tournament's Best Young Player as Argentina won the competition in Qatar.

His half-season at the Estádio da Luz ended on 31 January 2023, when Chelsea triggered his release clause in a deal worth around €121 million, then a British transfer record and by some distance the largest sale in Benfica's history.