Cancelo suffered a knee ligament injury in late August 2017 while on international duty, going on to be sidelined for one-and-a-half months. He returned to action during the 3–2 home victory over A.C. Milan in the Derby della Madonnina, featuring 20 minutes. After a few weeks of adpation in the Serie A, Cancelo made his debut as a starter at the Coppa Italia in a home victory against Pordenone. On 17 April 2018, he scored his first league goal with a free kick in a 4-0 home victory over Cagliari. During his phase of adaptation in Serie A, in which was added some tactical misunderstanding, his performances progressively improved, leading him to be included in Serie A's Team of the Year. Despite his good performances during the season, the club opted to not buy Cancelo.
On 27 June 2018, Cancelo was signed by Juventus on a five-year contract for €40.4 million, making his domestic league debut on 18 August in a 3–2 away win against Chievo. He won his first trophy with the club in January 2019, featuring the entire 1–0 victory over Milan for the Supercoppa Italiana. He scored his first league goal the same month, as his team came from behind to defeat Lazio 2–1 at the Stadio Olimpico in Rome; he also helped win the decisive match-winning penalty later during the same game, which was subsequently converted by compatriot Cristiano Ronaldo. On 6 October, Cancelo provided an assist for Rodrigo Bentancur in a 2–0 away win over Udinese. On 7 December, Cancelo provided an assist for Mario Mandžukić in a 1–0 home win over against his former club Inter Milan in the Derby d'Italia.
In May 2018, Cancelo was included in a preliminary 35-man squad for the finals in Russia, but he did not make the final cut.