He played college football for the Penn State Nittany Lions, and was selected by the Cowboys in the second round of the 2010 NFL draft.

Lee's older brother Conor was the placekicker for the University of Pittsburgh and his sister Alexandra was a student athlete at Upper St. Clair High School.

[2] In football, Lee rushed for 1,240 yards and 21 touchdowns while registering 95 tackles and four interceptions as a safety for an 11-1 squad his senior year.

Heading into 2008, Lee was a starting outside linebacker for coach Joe Paterno's Nittany Lions for two consecutive seasons.

In April 2008, Lee tore the anterior cruciate ligament in his right knee during a non-contact drill at spring practice.

[4] While rehabbing, he opted to serve as an undergraduate assistant coach, participating in every practice and wearing a headset on the sidelines during games that season.

It was speculated that his considerable fall from the first round was due to his history of injuries, that included a torn ACL on the right knee and partially torn ACL on the left knee during his last two seasons at Penn State, and throughout his career, injuries had indeed prevented Lee from playing a full season's slate of NFL games.

[13][14] Promoted to starting inside linebacker in 2011, Lee thrived immediately in new defensive coordinator Rob Ryan's scheme.

His key interception of Rex Grossman and fumble recovery in the final minute of the Cowboys' Monday Night Football game versus the Washington Redskins were crucial in the 18-16 comeback.

[22] On May 27, Lee tore his ACL for the third time in his career after being blocked to the ground by rookie offensive lineman Zack Martin during an organized team activity (OTA).

In the second game against the Philadelphia Eagles, he had 16 tackles (2 for loss), two passes defensed, an interception in the end zone, and sealed the 20–10 win with an onside kick recovery, although he also suffered a concussion.

Lee was named to the Pro Bowl as an injury replacement for Kansas City Chiefs linebacker Justin Houston.

[26] He was named to his second straight Pro Bowl as an injury replacement for Carolina Panthers linebacker Luke Kuechly.