The Commodores played their home games at Vanderbilt Stadium in Nashville, Tennessee, and competed in the Eastern Division of the Southeastern Conference (SEC).

They were led by interim head coach Todd Fitch, who replaced Derek Mason after his firing on November 29, 2020.

On November 28, in game against Missouri, Vanderbilt's Sarah Fuller became the first woman to play in a Power Five conference game by delivering the opening kickoff for the second half.

Fuller, the Commodores' goalkeeper on the school's SEC championship women's soccer team, was added to the football roster after the team's regular kicking specialists had to be quarantined due to COVID-19 protocols.

[3][4] Listed in the order that they were released In the preseason media poll, Vanderbilt was predicted to finish in last place in the East Division.