On 12 July 2018, Lenglet joined Barcelona when they triggered his release clause of €35 million. He played the full 90 minutes for Barcelona as he helped them beat his former club Sevilla 2–1 in the 2018 Supercopa de España. On 23 September, Lenglet was sent off in his La Liga debut against Girona following an elbow on Pere Pons. He scored the winning goal in their Copa del Rey game against Cultural Leonesa in 1–0 win. He scored his first goal for Barcelona in La Liga against Real Sociedad at the Camp Nou. He provided an assist for compatriot Antoine Griezmann for Barcelona's first goal in a 3–0 win against Eibar away at the Ipurua on 19 October. Lenglet scored his first Champions League goal for the club on 8 August 2020, with a 10th minute header in a 3–1 victory at home against Napoli in Barcelona's round of 16 second leg match.