The season began on September 1 and concluded with its conference championship game on Saturday, December 3 at Ford Field in Detroit, Michigan.

In the 2021 MAC Championship Game, Northern Illinois defeated Kent State by a final score of 41–23.

Northern Illinois advanced to the Cure Bowl, where they lost to Coastal Carolina, 41–47.

Defending MAC champion Northern Illinois was named the preseason favorite.

The following individuals received postseason honors as voted by the Mid-American Conference football coaches at the end of the season.