Hightower played college football for the Alabama Crimson Tide, receiving consensus All-American honors and winning two BCS National Championships.

He collected 98 tackles, two sacks, and seven forced fumbles as a linebacker and caught 18 passes for 253 yards and four touchdowns at tight end.

[31] Head coach Bill Belichick named him the opening day starter, alongside Jerod Mayo and middle linebacker Brandon Spikes.

[32] He made his first career start and professional regular season debut in the New England Patriots' season-opener at the Tennessee Titans and recorded five combined tackles and returned a fumble recovery for a six-yard touchdown during their 34–13 victory.

[33] On September 30, 2012, he recorded two solo tackles and made his first career sack on quarterback Ryan Fitzpatrick, before leaving in the first half of their 52–28 victory at the Buffalo Bills due to a hamstring injury.

[35] In Week 7, Hightower collected a season-high seven solo tackles and sacked Mark Sanchez as the Patriots defeated the New York Jets 29–26 in overtime.

[37] He finished the 2012 season with 60 combined tackles (43 solo), four sacks, three pass deflections, two fumble recoveries, and a touchdown in 14 games and 13 starts.

[38] The New England Patriots finished the 2012 season atop the AFC East with a 12–4 record, clinching home field advantage and a first round bye.

[39] On January 13, 2013, Hightower started his first career playoff game and recorded three combined tackles in the Patriots' 41–28 victory against the Houston Texans in the Divisional Round.

[40] The following week, he made three combined tackles as the Patriots lost 28–13 to the eventual Super Bowl champions, the Baltimore Ravens, in the AFC Championship.

[41] Defensive coordinator Matt Patricia retained Hightower, Mayo, and Spikes as the starting linebackers to begin the 2013 regular season.

[43] The following week, he collected ten combined tackles (five solo) and sacked quarterback Ryan Tannehill in the Patriots' 27–17 win against the Miami Dolphins.

[50] On September 14, 2014, Hightower recorded eight combined tackles, broke up a pass, and had two sacks on Matt Cassel during the Patriots' 30–7 victory at the Minnesota Vikings.

In Week 13, Hightower recorded ten combined tackles (four solo) and a sack on Aaron Rodgers during a 26–21 loss at the Green Bay Packers.

[54] Hightower finished the 2014 season with 89 combined tackles (51 solo), six sacks, two pass deflections, and a forced fumble in 12 games and 12 starts.

[55] The New England Patriots finished atop the AFC East with a 12–4 record and clinched home field advantage and a first round bye.

[57][58] On February 1, 2015, Hightower started in Super Bowl XLIX and recorded five combined tackles during the Patriots' 28–24 victory against the Seattle Seahawks.

He made a key play near the end of the fourth quarter, tackling Marshawn Lynch at the one-yard line to prevent a touchdown that would have given the Seahawks the lead, and likely the title.

Because Butler caught the ball inside the one yard line, Hightower ensured he got out of the end zone to prevent a safety.

[61] In Week 2, Hightower recorded a season-high 12 combined tackles (eight solo) and was credited with half a sack during a 40–32 win at the Buffalo Bills.

[76] The New England Patriots finished atop the AFC East and clinched a first round bye and a playoff berth with a 14–2 record.

[78][79] On February 5, 2017, Hightower appeared in Super Bowl LI and helped the Patriots overcome a 25-point deficit and defeat the Atlanta Falcons 34–28 in overtime.

Hightower recorded two solo tackles, one sack, and forced a fumble deep in Atlanta territory which was recovered by the Patriots to help make it a one-possession game.

He started the New England Patriots' season-opener against the Kansas City Chiefs, but left their 42–27 loss in the second quarter after sustaining a knee injury.

[97] During Super Bowl LIII against the Los Angeles Rams, Hightower finished with two sacks and a pass deflection as the Patriots won 13–3.

[99] In Week 8 against the Cleveland Browns, Hightower recovered a fumble lost by running back Nick Chubb and returned it for a touchdown in the 27–13 win.