On June 25, 2015, Lyles was selected with the 12th overall pick in the 2015 NBA draft by the Utah Jazz. He signed his rookie scale contract with the Jazz on July 7. Lyles averaged 3.0 points and 3.6 rebounds per game over the first two months of his rookie season. He began picking up his production with more steady minutes during the month of January, scoring in double figures for the first time on January 4 with 13 points against the Houston Rockets. On January 9, in a win over the Miami Heat, he recorded 10 rebounds for the first time, and on January 14, he scored a then season-high 19 points in a loss to the Sacramento Kings. On February 3, he was named a Rising Stars Challenge participant at the 2016 NBA All-Star Weekend, replacing the injured Nikola Mirotić on the World Team roster. On April 10, he scored a career-high 22 points in a 100–84 win over the Denver Nuggets.
Denver Nuggets (2017–2019)
On June 22, 2017, Lyles was traded, along with the draft rights to Tyler Lydon, to the Denver Nuggets in exchange for the draft rights to Donovan Mitchell. On December 2, 2017, he scored a season-high 18 points in a 115–100 win over the Los Angeles Lakers. On December 10, 2017, he scored a career-high 25 points in a 126–116 overtime loss to the Indiana Pacers. On January 5, 2018, he set a new career high with 26 points in a 99–91 win over the Utah Jazz.
San Antonio Spurs (2019–present)
On July 12, 2019, Lyles signed with the San Antonio Spurs. On February 6, 2020, Lyles had a double-double, scoring a season-high 23 points while grabbing 10 rebounds and two steals in an 125-117 loss against the Portland Trail Blazers. On February 29, 2020, Lyles scored 20 points, nine rebounds, two assists, four steals, and one block in a 114–113 win over the Orlando Magic. On March 2, 2020, Lyles got himself 20 points again, along with three rebounds, two assists, and one steal in a 116–111 loss against the Indiana Pacers. On July 15, 2020, Lyles was reported to have underwent an appendectomy and was expected to miss the remainder of the 2019–20 season.
Career statistics
NBA
Regular season
Playoffs
College
National team career
Lyles has represented both Canada and the United States. Until his sophomore year in high school, he had trained in the United States developmental pipeline. On the international stage, Lyles played for Canada's Junior men's national team. During the summer of 2013, Lyles, along with Tyler Ennis, led Canada to an all-time-best 6th-place finish at the 2013 FIBA Under-19 World Championship with Lyles coming in second to Ennis in scoring at the tournament.