Marlo Thomas was approached by ABC executive Edgar Scherick after he saw her in a screen test for a failed pilot; he gave her several scripts to read, but she rejected them because they all portrayed women as girlfriends, wives, or secretaries rather than independent characters pursuing their own dreams.

Thomas originally wanted to name the sitcom 'Miss Independence,' a nickname given to her by her parents.

Although never officially credited as an executive producer (that credit went to creators Bill Persky and Sam Denoff), Marlo Thomas acted as a de facto executive producer through her own company, Daisy Productions, which she formed specifically for the series and which was credited on-screen as the production company.

In the original 1965 pilot, Ted Bessell's character was named Don Blue Sky and was portrayed as Ann's talent agent who was part Cherokee, rather than her boyfriend Donald Hollinger as later established in the series.

Ann's parents were played by different actors in the unaired pilot: Harold Gould as her father and Penny Santon as her mother, before being replaced by Lew Parker and Rosemary DeCamp for the actual series run.

The show was filmed at Desilu-Cahuenga Studios in Hollywood (later known as Ren-Mar Studios and now Red Studios Hollywood), even though the story was set in New York City, with only exterior shots filmed on location in Manhattan over several days.

The pilot episode's plot, about Ann trying to adopt the stage name 'Marie Brewster' (combining her family name and hometown), was reused and recycled into the Season 1 episode 'What's in a Name?' aired November 17, 1966.

Marlo Thomas insisted that the finale leave Ann and Donald engaged rather than married, not wanting to send young female viewers the message that marriage was the ultimate goal, so as not to undercut the show's feminist message.