He played college football for the Purdue Boilermakers as a defensive end and was selected by the New Orleans Saints in the fifth round of the 2006 NFL draft.

[5] As a freshman, he recorded 36 tackles and seven sacks as the 2002 Joliet Wolves football team won the NJCAA national championship.

[6] During the summer prior to his sophomore year, Ninkovich worked with his father, an ironworker, hanging beams on a Chicago construction site 19 stories high.

[6] In an October 2 contest against Notre Dame, Ninkovich recorded two sacks on defense and also caught a goal-line touchdown pass from Kyle Orton.

[6] He recorded four sacks against Indiana for the second straight season, giving him two of the three individual four-sack performances in school history.

[7] Throughout training camp, Ninkovich competed against Charles Grant, Willie Whitehead, and Eric Moore for the job as the starting defensive end.

During the game, Ninkovich recorded two sacks and two forced fumbles but was also flagged for an unnecessary roughness penalty which led to a Cowboys' touchdown.

Head coach Sean Payton named Ninkovich the backup defensive end to Will Smith and Charles Grant to begin the regular season.

[5] He made his professional regular-season debut during the Saints' season-opener at the Cleveland Browns and recorded three combined tackles during their 19–14 victory.

[11] On September 25, 2006, Ninkovich suffered a torn MC ligament in his knee while appearing on special teams during the Saints 23–3 victory over the Atlanta Falcons on Monday Night Football.

[12] On September 29, 2006, the Saints placed Ninkovich on season-ending injured reserve after he underwent surgery to repair the torn ligament.

[13] Ninkovich saw stiff competition[citation needed] throughout training camp, competing with Josh Cooper, Anton Palepoi, Jonathan Hamm, and Willie Evans.

Head coach Cam Cameron named him the backup defensive end to Jason Taylor and Matt Roth.

[citation needed] Throughout training camp, he competed against Charlie Anderson, Kelly Poppinga, Quentin Moses, Titus Brown, and Keith Saunders for the role of backup outside linebacker.

[39] During the 2012 offseason, Ninkovich moved to defensive end; his replacement at outside linebacker was Patriots rookie Dont'a Hightower.

Ninkovich had two forced fumbles in a game against the Denver Broncos and a game-ending overtime strip sack against the New York Jets.

[47] In the Patriots' 28–24 win over the Seattle Seahawks in Super Bowl XLIX, which happened to take place on his 31st birthday, Ninkovich sacked Russell Wilson once and recorded six tackles.

[48] Ninkovich started all 16 games for the Patriots in the 2015 season, recording 52 total tackles, 6.5 sacks, seven passes defended, and one forced fumble.

[53] In a postgame interview with WBZ Sports,[54] Ninkovich claimed the Patriots "broke down" in the locker room at halftime, resolving afterwards to play "one heck of a 30-minute half."