[4] In March, Zack Reed announced his second campaign for mayor after his unsuccessful run in 2017, followed by Kevin Kelley[7] and Landry M. Simmons in April,[13] and Sandra Williams in May.

[9] Dennis Kucinich, a longtime presence in Cleveland politics who had been rumored to be considering a run, announced his candidacy on June 14, 2021, two days before the deadline for submitting signatures to the Cuyahoga County Board of Elections.

Every candidate except DiBello labeled crime as the preeminent issue of the race, which had reached record levels during the COVID-19 pandemic, including a 24% increase in assaults with firearms compared to 2020.

[29] The issues of economic development, education, and government accountability and accessibility were also given attention, the latter in particular received emphasis due to the conviction of longtime Cleveland City Councilman Ken Johnson in late July 2021 on federal corruption charges[30] as well as the Ohio nuclear bribery scandal.

[33][34] State legislators Local officials Individuals Organizations Newspapers Labor unions Federal politicians Individuals Labor unions State legislators County officials Organizations Labor unions Due to both primary winners finding their strongest support in the West Side of Cleveland, both campaigns paid significant attention to the predominantly African-American East Side, where although Bibb was the best performing candidate, a majority of voters cast ballots for candidates other than Bibb or Kelley in the primary.

[61] Bibb campaigned as a progressive who would change how the city works as mayor, while Kelley presented himself as a moderate and experienced politician who would be prepared to lead from the start of his tenure.