On June 21, 2018, Sexton was selected with the eighth overall pick by the Cleveland Cavaliers in the 2018 NBA draft. He was the highest-selected player from Alabama since Antonio McDyess in 1995. On July 6, 2018, Sexton made his NBA Summer League debut. He recorded 15 points to go along with 7 rebounds. On October 17, 2018, Sexton made his NBA debut, coming off the bench for the Cleveland Cavaliers with nine points and three rebounds in a 104–116 loss to the Toronto Raptors. On November 24, 2018, Sexton scored a then career high 29 points against the Houston Rockets in a 117–108 victory. On December 9, 2018, he scored a season-high 29 points against the Washington Wizards in a 116–101 victory. On March 8, 2019, Sexton passed Kyrie Irving for 3 pointers made as a Cavs rookie with 76 against the Miami Heat. He also eclipsed 1,000 career points. On March 11, 2019, Sexton had 28 points against the Toronto Raptors in a 126–101 victory, to go along with 5 assists and 4 rebounds. In the week of March 8, 2019, Sexton had the best week of his rookie campaign, averaging 26.0 points, 3.8 assists, and 2.5 rebounds. During a stretch from March 8 to 22, he became the first rookie to score 23+ points in seven consecutive games since Tim Duncan in 1998, as well the only rookie in franchise history to successively score at least 23 points. Additionally, he is the only rookie in NBA history to have played at least 2,000 minutes while scoring over 16 points per game on over 40% 3-point accuracy and fewer than 3 turnovers. He was named to the Rising Stars Game at the 2020 NBA All-Star Weekend as a replacement for injured Miami Heat rookie Tyler Herro, where he put up 21 points, 5 rebounds and 3 assists for Team USA.