2016–17

The Buffalo Bills selected Lawson in the first round with the 19th overall pick in the 2016 NFL Draft.^[11]

On May 17, 2016, Lawson underwent shoulder surgery after tweaking it during offseason drills and was ruled out 4 to 6 months.^[12]

On June 6, 2016, the Bills signed Lawson to a four-year, $10.27 million contract that includes $9.82 million guaranteed and a signing bonus of $5.67 million.^[13]

On August 30, 2016, Lawson was placed on the reserve/physically unable to perform list.^[14] He was activated to the active roster on October 21, 2016.^[15] Lawson recorded his first NFL sack against the New England Patriots in Week 8.

In 2017, Lawson started 10 out of 11 games played, recording 33 tackles and four sacks. He suffered an ankle injury in Week 13 and was placed on injured reserve on December 5, 2017.^[16]

2018

Lawson started the 2018 season as the backup to free-agent signing Trent Murphy, but still retained significant playing time as the Bills rotated their defensive personnel throughout games. Lawson started several games after Murphy struggled with injuries. He recorded seven tackles in a Week 9 loss to the Chicago Bears.^[17] Against the Jacksonville Jaguars in Week 12, Lawson was involved in a fistfight with Jaguars running back Leonard Fournette as part of a brawl that broke out between the two teams in the third quarter. Lawson and Fournette were both ejected from the game for the scuffle, but while Lawson only received a $33,425 fine, Fournette was suspended for one game.^[18] Lawson later stated he was defending himself and his teammates and that Fournette initiated the fight.^[19]

Against the Miami Dolphins in Week 17, Lawson collected two sacks on Ryan Tannehill in addition to a forced fumble, making this his first career multi-sack game. He finished the 2018 season with much-improved stats, recording 30 combined tackles, four sacks, two fumbles forced, and six passes defended on the year.^[20] He was also named by Pro Football Focus to their team of the week after a strong performance against the Detroit Lions in week 15.^[21]

2019

On May 1, 2019, the Bills declined the fifth-year option on Lawson's contract, making him a free agent in 2020.^[22] Against the Denver Broncos in week 12, Lawson recorded two sacks on quarterback Brandon Allen after Broncos lineman Connor McGovern told Lawson he'd "never heard of him".^[23] Lawson finished the season with a career-high 6.5 sacks.^[24]