Ms. Pac-Man originally started out as an unlawfully modified version of the Pac-Man arcade game called "Crazy Otto". Crazy Otto was bought by Pac-Man's North American distributor Midway, and rebranded as Ms. Pac-Man.

The protagonist's name was originally going to be rendered as "Miss Pac-Man", but the developers then realized that because she was married and had a child, the "Miss" honorific was grammatically incorrect and would also imply she conceived out of wedlock, so the name was changed to "Ms. Pac-Man" (pronounced "Mizz Pac-Man"). However, this didn't stop future Pac-Man-centric games from mispronouncing the first part as "Miss", such as the Mario Kart GP games and Pac-Man World 3 among a few others.

In 2019, AtGames, a company specializing in replica microconsoles containing compilations of retro or retro-styled games, acquired a portion of the rights to Ms. Pac-Man from General Computer Corporation, the company that made the original Ms. Pac-Man game for Midway and Namco - this led to a lawsuit over the IP, with an undisclosed turnout. After this, Ms. Pac-Man would begin to disappear from Pac-Man games, implying that AtGames won the case, with Ms. Pac being replaced by a character named Pac-Mom, who has a visual design resembling Ms. Pac-Man's mother from Pac 'N Roll.

Pac-Mom first appeared in the Arcade Archives release of Pac-Land through graphical modification to the original ROM, and would then be named for the first time in Pac-Man Museum+ alongside modifications to other games that originally featured Ms. Pac-Man such as Pac-in-Time, and would appear again in Pac-Man World: Re-Pac in place of Ms. Pac-Man.

Ms. Pac-Man's final appearance in an original title would be on the Pac-Land stage in 2018's Super Smash Bros. Ultimate.