Fall 2021 Detroit City FC season

It was also the team's third and final season in the National Independent Soccer Association.

[1] Details for the 2021 NISA Independent Cup were released on June 10.

[9] Detroit was placed in the Great Lakes Region for the second straight year along with Rust Belt Derby rivals FC Buffalo, Cleveland SC, and Midwest Premier League side Livonia City FC.

City won the regional title for a second straight season after beating Cleveland, 4–1, in its third match.

Details regarding the Fall season were released on June 16.