Councillors Andrea Campbell, Annissa Essaibi George, Kim Janey, and Michelle Wu ran in the mayoral election, while Matt O'Malley did not seek re-election.

Councillors Ricardo Arroyo, Frank Baker, Kenzie Bok, Liz Breadon, Lydia Edwards, Michael F. Flaherty, Ed Flynn, and Julia Mejia ran for re-election; all eight were successful.

[1][2] On January 7, 2021, President-elect Joe Biden announced that he would select Walsh to serve as the United States Secretary of Labor.

[3] Walsh resigned as mayor on March 22, after being confirmed as Secretary of Labor, and was replaced as acting-mayor by Kim Janey, who also served as president of the Boston City Council.

[11] Other candidates in the election included: Althea Garrison, the first openly transgender person to serve in a state legislature and former member of the city council; Ruthzee Louijeune, a lawyer who worked as senior counsel for Senator Elizabeth Warren's presidential and senatorial campaigns; Erin Murphy, a former teacher in the Boston Public Schools; Alex Gray, a policy analyst; and Nick Vance, a political action co-chair of the NAACP in Boston.

Councillor Lydia Edwards, who was first elected to the city council in 2017, announced that she would run for reelection and launched her campaign on February 26, 2021, at a virtual event.

Councillor Frank Baker, who was first elected in 2011, announced that he would run for reelection after initially wanting to leave politics until the COVID-19 pandemic changed his plans.

Councillor Liz Breadon, who joined the council in 2020, ran for reelection against Michael Bianchi and entrepreneur Eric Porter.