Parsons played college football for the Penn State Nittany Lions, where he was named a consensus All-American, Big Ten Linebacker of the Year and the Cotton Bowl Defensive MVP as a sophomore in 2019.

On December 19, it was reported that Ohio State had committed NCAA violations because the university allowed him on the set of ESPN's College GameDay to take a picture with analyst Kirk Herbstreit.

As Herbstreit is a former Ohio State University quarterback, this was a violation of NCAA rules, as recruits are not allowed to have contact with members of the media associated with former student-athletes.

He finished second in the Big Ten Freshman of the Year voting behind wide receiver Rondale Moore.

Prior to the start of his sophomore season, Parsons was named to the Butkus Award preseason watch list.

He started 12 out of 13 games at middle linebacker, totaling 109 tackles (14 for loss), five sacks, 26 quarterback hurries, five deflected passes, and four forced fumbles.

[12] Parsons was named the 2019 Cotton Bowl Classic defensive MVP after recording 14 tackles, two sacks, and two forced fumbles.

[13] He opted out of the 2020 season due to concerns regarding the COVID-19 pandemic and declined his remaining years of college eligibility in favor of making himself available to the NFL in the 2021 draft.

[20] When DeMarcus Lawrence broke his foot in practice before Week 2, Dallas converted Parsons back to his high school position of defensive end where he saw immediate success, particularly as a pass rusher.

His 12 sacks in his first 13 career games are the fourth-most by a rookie in NFL history behind only Julius Peppers (13), Reggie White (13) and Leslie O'Neal (12.5).

[24] He was voted into the Pro Bowl, named first-team All-Pro by the Associated Press, and was the unanimous Defensive Rookie of the Year.

[42] Parsons cited the risk that COVID-19 presented to the health and well-being of his son Malcolm as a major factor in his decision to opt out participation in the 2020 college football season.

[48] In response, Parsons expressed disappointment that the US did not secure the release of Paul Whelan, a former U.S. Marine held in Russia, as part of the prisoner swap.

Discovery, making him president of their American football digital sports media division, B/R Gridiron.