The series was originally developed as a spin-off/continuation of Tina Fey's 30 Rock, with Alec Baldwin set to reprise his role as Jack Donaghy, following his political career in New York City.

After about a year of negotiations, Alec Baldwin dropped out of the project and was replaced by Ted Danson, whose character Neil Bremer was initially conceived as an older version of Jack Donaghy.

Because Ted Danson refused to relocate from Los Angeles to New York, the series was rewritten to be set in Los Angeles instead of New York City.

NBC gave the untitled Tina Fey and Robert Carlock comedy a 13-episode straight-to-series order in July 2019 before it was later named Mr. Mayor in May 2020.

A first-look teaser of the series was included as an end tag on the Peacock stream of "30 Rock: A One-Time Special," uploaded on July 16, 2020.

Production was suspended on March 12, 2020 due to the emergence of COVID-19, and filming was halted again on December 14, 2020 after several crew members tested positive for the virus.

Due to the pandemic disruptions, filming for the first season never resumed as planned in January 2021, resulting in the season being cut four episodes short, ending at nine episodes instead of the original thirteen ordered.

A holiday special titled "Mr. Mayor's Magical L.A. Christmas" aired on December 15, 2021, serving as the second season's premiere ahead of its regular time slot debut in March 2022.