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The Dallas Cowboys finished first in the NFC East with a 10–6 record and earned a playoff berth. On January 5, 2019, Vander Esch started in his first career playoff game and recorded ten combined tackles (six solo) as the Cowboys defeated the Seattle Seahawks 24–22 in the NFC Wildcard Game.

In week 4 against the New Orleans Saints, Vander Esch recorded a team high 11 tackles in the 12-10 loss. He missed Weeks 12-16 with a nerve issue in his neck before deciding to undergo surgery to correct the issue. He was placed on injured reserve on December 24, 2019.

The Dallas Cowboys selected Vander Esch in the first round (19th overall) of the 2018 NFL Draft, and he was the third linebacker selected.

He finished his first season in 2018 with a franchise rookie-record 140 combined tackles (102 solo), seven deflections, and two interceptions in 16 games and 11 starts. Vander Esch finished with the third most tackles among all players in 2018, behind Indianapolis Colts' linebacker Darius Leonard (163 tackles) and Green Bay Packers' linebacker Blake Martinez (144 tackles). He received an overall grade of 87.5 from Pro Football Focus in 2018, which ranked fourth among all qualifying linebackers.

As a junior in 2017, Vander Esch became a starter at weak-side linebacker and had a breakout season. He was named the Mountain West Defensive Player of the Year after making 141 tackles (fifth in the FBS), four sacks, two interceptions, and four forced fumbles (led the team). After the season, Vander Esch opted not to play as a senior (fifth-year) for the Broncos in 2018 and entered the 2018 NFL Draft. He finished his collegiate career with 188 tackles, five sacks and three interceptions.

On December 21, 2017, Vander Esch announced his decision to forgo his remaining eligibility and enter the 2018 NFL Draft. Vander Esch attended the NFL Scouting Combine at Indianapolis in late February and completed all of the combine and positional drills. Vander Esch's overall combine performance impressed scouts as he finished tied for second among all linebackers in the vertical jump and short shuttle. He also tied for fifth among his position group in the broad jump and finished fifth among linebackers in the three-cone drill.

Vander Esch walked on at Boise State University, 150 miles (240 km) south of Riggins. As a redshirt freshman in 2015, he appeared in all twelve games as a backup linebacker and registered 20 tackles (14 solo), one sack, one fumble recovery, and a first down on a fake punt. As a sophomore in 2016, he was limited to six games due to a neck injury, returning in the twelfth game against Air Force; he tallied 27 tackles (23 solo), 3.5 tackles-for-loss, one sack, and one interception.

Born and raised in Riggins, Idaho, Vander Esch is of Dutch descent. He attended Salmon River High School in Riggins, and competed in eight-man football, basketball, and track. His graduating class of 2014 had eleven students.

He made his professional regular season debut in the Cowboys' season-opener at the Carolina Panthers and recorded three combined tackles in their 16–8 loss. On September 30, Vander Esch earned his first career start after Sean Lee sustained a hamstring injury and was inactive for three games (Weeks 4–6). He made six combined tackles as the Cowboys defeated the Detroit Lions 26–24. The following week, he collected 14 combined tackles (11 solo) during their 19–16 loss at the Houston Texans in Week 5. On November 11, Vander Esch recorded a season-high 13 solo tackles and made his first career interception during a 27–20 win over the Philadelphia Eagles, earning him NFC Defensive Player of the Week. He intercepted a pass by Eagles' quarterback Carson Wentz, that was intended for tight end Zach Ertz, during the first quarter. The following week, Vander Esch recorded eight combined tackles, a season-high three pass deflections, and intercepted a pass by Falcons' quarterback Matt Ryan during a 22–19 win at the Atlanta Falcons in Week 11. In Week 16, he collected a season-high 15 combined tackles (11 solo) as the Cowboys defeated the Tampa Bay Buccaneers 27–20.

Leighton Vander Esch (born February 8, 1996) is an American football linebacker for the Dallas Cowboys of the National Football League (NFL). He played college football at Boise State University.