Creator Amy Sherman-Palladino drew inspiration for the series from childhood memories of her father, who was a standup comedian based in New York City, as well as from her admiration for early female comics such as Joan Rivers and Totie Fields.

Jason Ralph, who plays producer Mike Carr, is the real-life husband of star Rachel Brosnahan.

Milo Ventimiglia and Kelly Bishop, who both guest-starred in season 4, previously appeared together on Gilmore Girls, another series created by Amy Sherman-Palladino.

Filmmaker John Waters appeared as a guest star during the show's fourth season.

The exterior of the Gaslight Club was filmed outside 96 St. Mark's Place in the East Village, the same building featured on the cover of Led Zeppelin's 1975 album Physical Graffiti.

The interior scenes for the B. Altman department store were shot in a disused bank in Brooklyn, while the garment factory interiors were filmed at Martin Greenfield Clothier in Bushwick, even though the story places the factory in Manhattan's Garment District.

The show is known for its frequent use of 'oners,' extended single-shot scenes, including a two-minute sequence in 'Going to the Catskills' and a complex 12-page scene in 'Strike Up the Band' where Midge finds her parents fighting amid scattered clothes.

The design of a Cuban dance number in season 3, episode 5 was inspired by the 1964 film I Am Cuba, a favorite of the series' cinematographer M. David Mullen.

The apartments of Midge and her husband Joel, and of Midge's parents, were built on the same set, with Midge and Joel's apartment given a more modern late-1950s design inspired in part by Doris Day movies, according to production designer Bill Groom.

In December 2018, Amazon opened a pop-up restaurant in Manhattan modeled after a 1950s Carnegie Deli, serving sandwiches named 'The Maisel' and 'The Susie' with nothing costing more than 99 cents, with proceeds benefiting the Lower Eastside Girls Club.

To promote the show ahead of the 71st Primetime Emmy Awards, Amazon partnered with businesses near Santa Monica to sell goods at 1959 prices, including gasoline at $0.30 per gallon, which caused long queues and traffic jams requiring police intervention.

The show's distinctive costume and set design, particularly its women's hats and dresses, led the Paley Center for Media to create a dedicated exhibit called 'Making Maisel Marvelous' in 2019, and two of the series' costumes were acquired by the Smithsonian's National Museum of American History in December 2019.