He played college football at Florida Atlantic, and was selected in the third round of the 2017 NFL draft by the New Orleans Saints.

[2] Coming out of Florida Atlantic, Hendrickson was projected by the majority of NFL draft experts and scouts to be a third or fourth round pick.

On March 30, 2017, Hendrickson participated at Florida Atlantic's pro day, had 18 reps on the bench press, and performed positional drills.

Head coach Sean Payton named him the backup defensive end to Cameron Jordan and Alex Okafor to begin the regular season.

On September 17, 2017, Hendrickson made his professional regular season debut against the New England Patriots and recorded three combined tackles in the Saints' 36–20 loss.

[12] The following week, he earned two combined tackles and sacked Carolina Panthers quarterback Cam Newton during a 34–13 victory.

[15] In the 2019 regular season opener for the Saints, Hendrickson recorded two sacks against the Houston Texans on Monday Night Football.

[17] In Week 9 of the 2020 season against the Tampa Bay Buccaneers, Hendrickson recorded two sacks on Tom Brady during the 38–3 win.

He had his only multi-sack game of the season in Week 5 against the Green Bay Packers, sacking Aaron Rodgers twice for loss.

[27] Hendrickson netted another sack in the AFC Championship Game against the Chiefs, leading the Bengals defensive charge on the way to their third Super Bowl appearance in team history.

[28] Hendrickson recorded one sack in Super Bowl LVI, with the Bengals losing 23–20 to the Los Angeles Rams.

Hendrickson had his first breakout game of the season in Week 3 against the Rams, sacking Matthew Stafford twice, and recording seven total tackles.

[46] He led the league with 17.5 sacks, along with 46 tackles, six passes defensed, and two forced fumbles, and was named first-team All-Pro for 2024.