On December 17, 2020, Purdue announced that defensive coordinator Bob Diaco would not return to the coaching staff.

[1] On January 10, 2021, the school hired Mark Hagen as defensive line coach, replacing Terrance Jamison.

On June 16, Jeff Brohm announced that Lambert, English, and Hagen would all serve as co-defensive coordinators in addition to their regular coaching duties, with Lambert making the game-day play calls.

[5] Former graduate assistants Justin Sinz and TJ McCollum would move to recruiting positions.

Sources: The 2021 schedule consists of 6 home and 6 away games in the regular season.