He played college football for the Penn State Nittany Lions, earning unanimous All-American honors as a senior in 2015.

[5] Nassib enrolled at Pennsylvania State University and joined the Nittany Lions team as a walk-on in 2011.

[13] Nassib was named a unanimous All-American and the Big Ten's Nagurski-Woodson Defensive Player of the Year for 2015.

[23] In his first game as a professional, against the Philadelphia Eagles, Nassib recorded one sack, three tackles, and one deflected pass, and earned a nomination for Pepsi NFL Rookie of the Week.

[31] In the Raiders' 2021 season opener against Baltimore, broadcast on Monday Night Football, Nassib strip sacked Ravens quarterback Lamar Jackson in overtime, which Las Vegas recovered to set up the winning touchdown in a 33–27 win.

[5] On June 21, 2021, during Pride Month,[1] Nassib released a statement on his Instagram account stating that he is gay, becoming the first active NFL player to come out publicly.

[1][44] In the statement, he pledged to donate $100,000 to The Trevor Project, a crisis intervention and suicide prevention organization for LGBTQ youth, and to continue to champion their work.

[3] That day, jerseys and T-shirts with his name were the top sellers among all NFL players at Fanatics, the league's sales partner.

[47][48][49] In April 2024, Nassib was joined by The Trevor Project founder Peggy Rajski to announce the Cleveland Browns’ second round draft pick on live TV.