He made his professional regular season debut and first career start in the Colts' season-opener against the Cincinnati Bengals and recorded nine combined tackles and recovered a fumble in their 34–23 loss. On September 16, 2018, Leonard collected a season-high 19 combined tackles (15 solo) and made his first career sack on Redskins' quarterback Alex Smith during a 21–9 win at the Washington Redskins. For his performance, he was named the AFC Defensive Player of the Week. The following week, Leonard recorded 13 combined tackles (nine solo) and made two sacks on Eagles' quarterback Carson Wentz in the Colts' 20–16 loss at the Philadelphia Eagles in Week 3. On October 4, 2018, after totaling 54 combined tackles (which led the league, and was most by a player in first four weeks of the season since 1994) and four sacks (leading all rookies) in September, Leonard was named the NFL Defensive Rookie of the Month. Leonard was inactive for the Colts’ Week 5 loss at the New England Patriots due to an ankle injury he sustained the previous week. On November 18, 2018, Leonard made seven combined tackles, one pass deflection, one sack, and his first career interception during a 38–10 victory against the Tennessee Titans in Week 11. Leonard intercepted a pass by Titans’ backup quarterback Blaine Gabbert, that was intended for wide receiver Tajae Sharpe, and returned it for a ten-yard gain during the third quarter. In Week 15, Leonard broke the Colts' franchise record for most tackles by a rookie in a single season with 143, in a 23–0 win vs the Dallas Cowboys. In Week 17, Leonard broke the Colts’ franchise record for most tackles in a single season with 163, in a 33–17 win vs the Tennessee Titans. For his performance, Leonard was once again awarded with AFC Defensive Player of the Week. Leonard was awarded the AFC Defensive Player of the Month award for December. He finished his rookie season in 2018 with 163 combined tackles (111 solo), eight pass deflections, seven sacks, and two interceptions in 15 games and 15 starts. Leonard recorded the most tackles among all players as a rookie in 2018. He received an overall grade of 80.3 from Pro Football Focus, which ranked ninth among all linebackers in 2018.
