[7] Notably, his first college sack came against future Buffalo Bills teammate Josh Allen during a game against Wyoming.

[8] Epenesa did not start any games during his sophomore season, but still broke into the double digits for sacks and returned a fumble recovery for a touchdown.

[11] Before his junior season, Epenesa was projected as a first-round pick in the 2020 NFL draft, with some estimations placing him as high as second.

[13] Following a junior season with 11.5 sacks, 4 forced fumbles, and 49 tackles, Epenesa announced that he would forgo his senior year and declare for the 2020 NFL Draft.

Epenesa, who is of Samoan ethnicity, was named to the preseason Polynesian College Player of the Year Watch List in 2018 and 2019.

[20] In Week 3 of the 2020 season, Epenesa recorded his first career sack in a 35–32 win over the Los Angeles Rams, tackling quarterback Jared Goff during the first quarter.

In week 5 of the 2022 season against the Pittsburgh Steelers, Epenesa was ejected from the game with one minute left after he elbowed referee John Hussey in response to being pushed by the former during a brief ruckus between the Bills and Steelers that began when Pittsburgh quarterback Kenny Pickett shoved Bills defender Shaq Lawson for a late hit.