The concept for the series was largely developed in a few hours when Hiromi Wakabayashi, who had been thinking about the idea for a while, pitched it to the staff of Gurren Lagann during a post-production relaxation trip; almost all concepts, including the names 'Panty' and 'Stocking', were coined at that very first meeting.

Hiromi Wakabayashi cited American adult animation such as Drawn Together as inspiration for the show's crude tone and visual style.

Many key staff members from Gurren Lagann reunited for this project, including director Hiroyuki Imaishi and character designer Atsushi Nishigori.

The explosion scenes of enemies in the latter half of the story were filmed using a live-action tokusatsu-style technique rather than pure animation, reflecting the staff's desire to go beyond typical anime methods.

The animation combined two contrasting techniques: a heavily-drawn style for dynamic action (later reused in works like Kill la Kill) and a limited, parts-based animation style using software like After Effects for comedic scenes, aiming to create the illusion of large movement while minimizing the number of drawn frames.

Each episode's subtitle is a parody of a classic American film title, and the show is filled with parodies referencing various Japanese and American movies, anime, and manga.

The town of Romero and Carpenter Town, featured in episode 14, is named after horror directors George A. Romero and John Carpenter.

The series was selected as a jury recommended work in the animation division of the 15th Japan Media Arts Festival organized by the Agency for Cultural Affairs.

Panty & Stocking with Garterbelt was the last Gainax-produced anime to be broadcast in its entirety on analog terrestrial television in Japan.

Although Gainax originally produced the series, the copyright was later held by Colony until 2023, when Trigger officially announced it had acquired the rights and unveiled a new project, eventually leading to the 2025 sequel New Panty & Stocking with Garterbelt.

An English dub of the original series was produced, and the Blu-ray Box 'Forever Bitch Edition' released in 2013 included newly recorded English audio along with Japanese and English subtitles.