AfterMASH was developed as a vehicle for Harry Morgan, Jamie Farr, and William Christopher, as they were the only main cast members of M*A*S*H who wanted the series to continue when a vote was taken before the final season.

Larry Gelbart, who created and ran M*A*S*H for its first four seasons, also created AfterMASH, and Burt Metcalfe, the only producer to stay with M*A*S*H throughout its entire run, was involved in the spin-off's production.

Writer Ken Levine said a big reason he agreed to work on AfterMASH was the chance to work again with producer Burt Metcalfe and to learn from Larry Gelbart, calling the latter 'the absolute master.'

Doctor character Gene Pfeiffer (Jay O. Sanders) was suddenly dropped from the cast after the introduction of Dr. Mark Boyer (David Ackroyd), who had originally only signed on for two episodes but became a much larger presence, eventually becoming a full regular in season two.

Actress Barbara Townsend, who played Mildred Potter in season one, was replaced by Anne Pitoniak for season two.

Gary Burghoff reprised his Radar O'Reilly role in a season one two-part episode, and the character later got his own unaired pilot called W*A*L*T*E*R, which aired only once as a CBS special in July 1984 (and was pre-empted in some regions by the Democratic National Convention).

In the season one episode 'Chief of Staff,' Colonel Potter's office was redecorated with items from the 4077th MASH unit, including a portrait from the M*A*S*H episode 'Picture This,' and the original show's theme song was played.

According to Ken Levine, when the show's ratings dropped, a 20th Century Fox executive seriously suggested recasting Hot Lips Houlihan with a different actress (even floating Diana Ross) since Loretta Swit had declined to return, an idea the writers rejected as absurd.

Despite its later reputation as one of the worst shows ever (named by Time in 1999 and TV Guide in 2002), AfterMASH's first season finished in the Top 15 of the year-end Nielsen ratings, and the episode 'Fallout,' about atomic testing victims, was nominated for an Emmy and won its writer-director Larry Gelbart a Peabody Award.

For season two, CBS moved AfterMASH to Tuesday nights opposite NBC's The A-Team and ran a marketing campaign with illustrations of Klinger in a nurse's uniform shaving Mr. T's mohawk, betting it would steal viewers—but ratings instead plummeted and the show was cancelled after only nine season-two episodes.

Unlike its parent series, AfterMASH has never been released on home media, was never rerun in syndication, and has never been officially available on streaming, with only unofficial off-air recordings circulating.