Hernandez started his career with Atlético Madrid, where he made more than 100 competitive appearances, reaching the 2016 UEFA Champions League final.

[12][13] On 9 November 2013, while still a junior, he was called up by manager Diego Simeone for a La Liga match against Villarreal,[14] but remained unused in the 1–1 away draw on the following day.

[17] Hernandez made his first-team debut on 3 December 2014, playing the full 90 minutes in a 3–0 away success over L'Hospitalet in the campaign's Copa del Rey.

[18] His maiden appearance in the Spanish top level took place on the 21st, when he came on as a late substitute for Guilherme Siqueira in a 4–1 away win against Athletic Bilbao.

[31] On 23 August 2020, along with his Bayern Munich teammates, Hernandez became a Champions League winner after a 1–0 victory over Paris Saint-Germain (PSG) in the final.

[38] On 9 July 2023, Hernandez signed for Ligue 1 club Paris Saint-Germain on a five-year contract until 30 June 2028, for a transfer fee reported to be in the region of €40 million.

[42] On 25 October 2023, Hernandez for the first time faced his younger brother, Théo, as an opponent playing competitive senior football in the Champions League group stage home game against AC Milan, a 3–0 win for PSG.

[43] In the first leg of the Champions League semi-finals away to Borussia Dortmund on 1 May 2024, Hernandez tore his anterior cruciate ligament (ACL) in his left knee, ruling him out for the rest of the season.

[44][45] Hernandez earned his first cap for France on 6 March 2012, playing the full 90 minutes for the under-16 team in 1–1 friendly draw against Italy at Coverciano.

[51][52] In October 2021, ahead of the UEFA Nations League semi-finals against Belgium, Lucas for the first time received a call-up to the national team from Didier Deschamps together with his brother Théo; the two were later fielded in the 3–4–1–2 formation as a left center back and a left wingback, respectively, making it the first time they played together in a senior competitive game, which turned out to be a 3–2 comeback victory for France, with Théo scoring the winning goal in the 90th minute.

[53] Hernandez was selected for France's squad ahead of the 2022 FIFA World Cup but suffered a ruptured anterior cruciate ligament 13 minutes into the first group match against Australia and was subsequently ruled out for the remainder of the tournament.

[59] 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.

[63][64] Hernandez was arrested again in June of the same year for violating the restraining order after he and Llorente landed together in Madrid, returning from their honeymoon.