[4][5] On 10 August 2013, manager Rémi Garde handed Tolisso his debut for the club, bringing him on as 92nd minute substitute in a 4–0 Ligue 1 home win over Nice, but he didn't even touch the ball once as the referee blew the whistle few seconds later.

[6][4] He made his European club competition debut on 24 October 2013, featuring in a 1–0 win over HNK Rijeka in the group stage of the 2013–14 UEFA Europa League.

[8] On 9 March 2014, he scored his first senior career goal with an injury time (in the 94th minute) winner to give Lyon a 2–1 Ligue 1 away win over Bordeaux.

[9] Tolisso was used as a utility player for the majority of the season, operating at right back in place of Mouhamadou Dabo and later in central midfield following injuries to Yoann Gourcuff and Gueïda Fofana.

[10] The continued absence of Fofana and subsequent injury to Clément Grenier afforded Tolisso the opportunity to enjoy more first team action with Lyon in the following season.

[11] At the end of the season Tolisso and teammates Nabil Fekir and Anthony Lopes were rewarded with improved contracts, penning new deals with the club until 2020.

[13] Tolisso's form in the previous season earned him numerous suitors from around Europe and in July 2016 he was subject to a €37.5 million bid from Serie A side Napoli.

The ill-discipline shown in Lyon's loss to Saint-Étienne prompted club president Jean-Michel Aulas to announce that both players would be severely punished for their actions.

[26][27] He made his debut for the club on 5 August, starting in a penalty shoot-out victory over Borussia Dortmund which saw Bayern crowned Supercup champions.

"[43] Having previously represented France at various youth levels, Tolisso was called up to the senior squad for the first time to face Luxembourg and Spain in March 2017.

[51] On 6 July, Tolisso started the quarter-final match against Uruguay and provided an assist to Antoine Griezmann's goal which saw France advance following a 2–0 victory.

[53] On 15 July, Tolisso appeared in the 73rd minute, again replacing Matuidi, as France defeated Croatia 4–2 in the final, to win their second World Cup title.