The series was originally announced under the title First Ladies when Showtime gave it a series order on February 5, 2020.

Pamela Adlon was originally cast in the series but was replaced by Judy Greer in February 2021 due to scheduling conflicts.

The show features an anthology structure with three storylines, each first lady played by two actresses depicting younger and older versions, including Jayme Lawson and Viola Davis as Michelle Obama, Kristine Froseth and Michelle Pfeiffer as Betty Ford, and Eliza Scanlen and Gillian Anderson as Eleanor Roosevelt.

Viola Davis was not only the star playing Michelle Obama but also served as an executive producer on the series alongside her husband Julius Tennon.

Filming for the series began on February 25, 2021, in Covington, Georgia.

The series received mixed reviews, holding a 41% approval rating on Rotten Tomatoes and a score of 50 out of 100 on Metacritic, with critics praising the performances, costumes, and set design but criticizing the pacing and plot.

Despite its starry cast, Showtime canceled The First Lady after just one season on August 1, 2022.