Detroit native, Nick Perry attended Mackenzie High School for most of his prep career; when Mackenzie was shuttered in 2007, Perry transferred to Martin Luther King High School for his senior season. During his Junior year in 2006, Perry was named to the All-metro and All-city teams while getting 75 tackles and 11 sacks. His senior year also brought great success as he played at defensive end, and Tight End. He recorded 147 tackles and a Michigan Record 36 Sacks. He also caught 14 passes for 310 yards and eight touchdowns. He received numerous honors including being named to the USA today All-USA First Team, Scout.com All-American second team, Super Prep All-Midwest, Prep-Star All Midwest, All-State and Detroit News All-Detroit and the Dream Team “MVP.” He Also participated in the 2008 U.S. Army All-American Bowl.
Perry was measured to be 6'4" and weighing in at 235 pounds coming out of King High School. He ran a 4.51 forty-yard dash, bench pressed 315 pounds, and squatted 400 pounds. He finished with a 3.3 Grade point average and received scholarship offers from Miami, Michigan, Michigan State, and USC. He ultimately decided to play at USC.
During his freshman year in 2008, Perry was redshirted as a defensive end.
Perry came on to the scene in 2009 as mainly as a backup defensive end playing mostly in passing situations. He appeared in 13 games and made his first start against Stanford Cardinal in a 55–21 defeat. He had 24 tackles, nine for a loss, with a team best nine sacks. His performance had him named to the 2009 Football Writers Freshman All-American first team.
Perry started nine games in his sophomore season in 2010, and saw action as a backup in others. He appeared in a total of 12 games, but missed the opener against The Hawaii Warriors with a sprained ankle. During this season he had 25 tackles with 7.5 of them for a loss. He also recorded four sacks, forced two fumbles, and recovered one.
During his final season as a Trojan in 2011, Perry recorded 54 tackles over 12 games, with 13 for a loss along with 8.5 sacks.
On December 16, 2011, it was announced that he would enter the 2012 NFL Draft. Perry was viewed to be a bit small to be a defensive end with a height of 6'3 and 250 pounds and was predicted to be moved to an outside linebacker in a 3-4 defense. He was stated to be an explosive player who can fire off the ball and get upfield in a hurry. He was also stated to have trouble with his lateral movement which will cause problems if he has to drop back in coverage as a linebacker. Perry's lack of bulk was also believed to make him an ineffective runstopper. Many scouts also believed that he was inconsistent. He was given a late first round grade. The teams that he was believed to be most likely to be selected by were the San Diego Chargers, the Cleveland Browns, Houston Texans, Green Bay Packers, San Francisco 49ers, and New England Patriots.
Perry was selected in the first round (28th overall) by the Green Bay Packers in the 2012 NFL Draft. Packers General Manager Ted Thompson commented that "“He’s got that kind of juice...", while Defensive coordinator Dom Capers stated “We think he can certainly fit into our nickel scheme, being an edge rusher there...Maybe we can move him around a little bit." Perry commented that “I’m ready to take it to the next level. It’s been a dream all my life. I’m taking my chance now.”.
Perry played in six games in the 2012 season and recorded two sacks. He was put on injured reserve after he suffered a wrist injury in week 6.
Perry had slightly more success in 2013, playing in 11 games, starting in 6 of them, and recording four sacks and forcing three fumbles.
In 2014, Perry played in 15 games, recording 3 sacks, including 2 in a game against the Minnesota Vikings. Even though he had an underwhelming season, Perry recorded 1.5 sacks in the Divisional Playoff Game against the Dallas Cowboys, which helped contribute to the victory.
On May 4, 2015, the Packers declined to pick up the fifth-year option on Perry's contract. The deadline was Sunday May 3.
Perry re-signed with the Packers on a one-year, $5 million contract on March 11, 2016.
On March 9, 2017, Perry signed a five-year, $60 million contract extension with the Packers.