[12] Two days later, he was called up to the first team for a La Liga match against Eibar due to injuries,[13] but remained an unused substitute in the 3–1 home win.

[14] On 4 August 2016, Hernandez extended his contract until 2021, being immediately loaned to fellow league club Deportivo Alavés for one year.

[19] A regular starter during the Basque team's run in the Copa del Rey, Hernandez helped them reach the final for the first time in their 91-year history.

[21][22][23] He made his competitive debut on 16 August, replacing Marco Asensio in a 2–0 home win against Barcelona for that year's Supercopa de España.

[24] Hernandez made three appearances during the 2017–18 edition of the UEFA Champions League,[25] helping the club win its third consecutive and 13th overall title in the competition.

[43] On 25 October 2023, Hernandez faced his older brother, Lucas, for the first time as an opponent playing competitive senior football in the UEFA Champions League group stage away game against Paris Saint-Germain, a 3–0 loss for Milan.

[47] On 6 October 2024, his 27th birthday, Hernandez had a controversial game in Florence, which ended in a 2–1 loss for Milan to Fiorentina, followed by his post-game argument with a referee that culminated in a red card and a subsequent two-game suspension.

[48] On 14 January 2025, he scored his 30th Serie A goal for Milan in a 2–1 away victory over Como, becoming the club's highest-scoring defender, surpassing Paolo Maldini's previous record.

[51] In October 2021, ahead of the UEFA Nations League semi-finals against Belgium, Théo for the first time received a call-up to the national team from Didier Deschamps together with his brother Lucas; the two were later fielded in the 3–4–1–2 formation as a left centre-back and a left wing-back, respectively, making it the first time they played together in a senior competitive game.

[52] On 7 October, he scored a late-time winner in the 3–2 victory against the aforementioned opponent, sending his team to the final for the first time in history of the tournament.

[60] In 2022, French newspaper L'Équipe found that Jean-François – who went missing in 2004 – was living in Thailand, and had allegedly been legally blocked by his ex-partner from seeing their children.