He played college football for the Illinois Fighting Illini, where he won the Ted Hendricks Award and the Bill Willis Trophy, and was selected by the Texans in the first round of the 2012 NFL draft.

He broke out during his junior season in 2011, leading the country in quarterback sacks (16) and forced fumbles (9) while primarily playing at the defensive end position.

Whitney attended Detroit Lions, Cleveland Browns, Buffalo Bills, Jacksonville Jaguars, and Dallas Cowboys.

[17][18] Throughout training camp, Mercilus competed to be a starting outside linebacker against Connor Barwin and Brooks Reed after the role was left vacant by the departure of Mario Williams.

[19] Head coach Gary Kubiak named Mercilus a backup outside linebacker to start the regular season, behind Connor Barwin and Brooks Reed.

During Week 7, Mercilus recorded three combined tackles, broke up a pass, and made his first NFL sack during a 43–13 win against the Baltimore Ravens.

[23] Mercilus entered training camp slated as a starting outside linebacker after Connor Barwin departed in free agency.

Head coach Gary Kubiak named Mercilus and Brooks Reed the starting outside linebackers to begin the regular season.

[33] Head coach Bill O'Brien retained Mercilus and Clowney as the starting outside linebackers to begin the regular season in 2015.

[34] During Week 8, Mercilus collected a season-high seven combined tackles and recorded 3.5 sacks as the Texans defeated the Tennessee Titans by a score of 20–6.

Head coach Bill O'Brien named Mercilus and Jadeveon Clowney the starting outside linebackers to begin the season, alongside Brian Cushing and Benardrick McKinney.

[41] During Week 5, Mercilus suffered a torn pectoral during a 42–34 loss to the Kansas City Chiefs on Sunday Night Football.

[44] In week 7 against the Jacksonville Jaguars, Mercilus forced his first fumble of the season on Blake Bortles which was recovered by teammate Jadeveon Clowney.

[45] In week 12 against the Tennessee Titans, Mercilus recorded a season high 5 tackles and sacked Marcus Mariota 1.5 times during the 34–17 win.

[50][51] During Week 3 against the Los Angeles Chargers, Mercilus forced Philip Rivers to fumble the football once as the Texans won on the road by a score of 27–20.

[53] During Week 15 against the Tennessee Titans, Mercilus intercepted a pass thrown by Ryan Tannehill off a deflection by Justin Reid and returned it for 86 yards during a 24–21 victory.

[56] In the AFC wild card game against the Buffalo Bills, he recorded a strip sack on quarterback Josh Allen which was recovered by teammate Jacob Martin during the 22–19 overtime win.

[65] On November 14, he suffered a torn bicep during a Week 10 game against the Seattle Seahawks;[66] the Packers placed him on injured reserve two days later.

[68] While initially expected to be lost for the year, Mercilus returned to practice following the regular season finale, and was officially activated from injured reserve on the eve of the team's divisional playoff game.

[71] Mercilus is the founder of the WithMerci Foundation, an organization that "advocates services and support for families of children with disabilities and special needs".