Maison Ikkoku was animated following the success of Urusei Yatsura, another Rumiko Takahashi manga that was being serialized at the same time, and many staff members from the Urusei Yatsura (1981) anime team moved on to work on this series.

Several voice actors from the Urusei Yatsura (1981) anime, including Kazunari Futamata, Sumi Shimamoto, Shigeru Chiba, Akira Kamiya, Yuko Mita, Toshio Furukawa and Saeko Shimazu, were cast in Maison Ikkoku, reusing much of the earlier show's cast.

The production suffered multiple changes of main staff during its run, including three different chief directors (Kazuo Yamazaki, Takashi Anno, and Naoyuki Yoshinaga) across the 96 episodes.

Unlike Urusei Yatsura, which frequently altered its story to match the broadcast season, Maison Ikkoku initially tried to stay very close to the source manga up through episode 26, which caused viewer complaints because episode content (like New Year's or summer festival scenes) no longer matched the actual broadcast season; from episode 27 onward, staff began swapping seasonal events to match the real air date.

Nijaidō Nozomi, a character who moves into room 2 in the manga, never appears in the TV anime at all, but he does appear in the 1988 theatrical film Maison Ikkoku: The Final Chapter.

An anime-original character named Zenzaburo Mikoshi was introduced in episode 50, temporarily occupying room 3 of Ikkoku-kan, a room that goes unused by anyone in the original manga (Godai later uses it temporarily too).

Shun Mitaka's car was changed from a Nissan Silvia in the manga to a Toyota Soarer in the anime, reportedly because Toyota became a sponsor of the show.

For episode 24 only, the opening and ending themes were replaced with Gilbert O'Sullivan's songs 'Alone Again (Naturally)' and 'Get Down,' tying in with the theatrical live-action Maison Ikkoku film starring Mariko Ishihara, which used the same songs; licensing issues reportedly forced the show to revert to its previous theme songs starting episode 25.

A producer at the time stated the reason for reverting was unclear, and a radio show later reported that Fuji TV claimed the original opening theme 'Kanashimi yo Konnichiwa' had suddenly risen on the Oricon charts, though no such chart surge actually occurred.

Songs were released under the name of the fictional heroine Otonashi Kyoko rather than under voice actress Sumi Shimamoto's own name, marking one of the earliest clear examples of a 'character song' explicitly marketed as sung by the in-story character rather than by the voice actor.

A drama CD series called 'Sound Theater' was produced using the TV series' soundtracks overlaid with narration by Shigeru Chiba (voice of Yotsuya); the narration was originally on the main audio track but was later moved to a secondary audio track so listeners could isolate the drama portions.