Anno’s third live-action film was Cutie Honey, based on Go Nagai’s 1973 manga and anime series. Released in the summer of 2004, this lighthearted fantasy/superhero film was a stark contrast to his earlier, more realist live-action works. Later in 2004, Anno supervised but did not direct the three-part OVA, Re: Cutie Honey, instead directed by Hiroyuki Imaishi (part 1), Takamichi Itō (part 2), and Masayuki (part 3).

Anno did not gain recognition until the release of his work on Hayao Miyazaki’s 1984 film Nausicaä of the Valley of the Wind. Running short on animators, the film’s production studio posted an ad in the famous Japanese animation magazine Animage, announcing that they were in desperate need of more animators. Anno, in his early twenties at the time, read the ad and headed down to the film’s studio, where he met with Miyazaki and showed him some of his drawings. Impressed with his ability, Miyazaki hired him to draw some of the most complicated scenes near the end of the movie, and valued his work highly.

Anno went on to become one of the co-founders of Gainax in December 1984. He worked as an animation director for their first feature-length film, Royal Space Force: The Wings of Honneamise (1987), and ultimately became Gainax’s premiere anime director, leading the majority of the studio’s projects such as Gunbuster (1988) and Nadia: The Secret of Blue Water (1990–1991). However, Anno fell into a four-year depression following Nadia — the series was handed down to him from NHK from an original concept by Hayao Miyazaki (of which Castle in the Sky is also partly based upon) and he was given little creative control.

In 1994, the minor planet 9081 Hideakianno was named after him by his old friend Akimasa Nakamura.

The show did not garner high ratings in Japan at its initial time slot, but after being moved to a later, more adult-oriented venue, it gained considerable popularity. Budgeting issues at Gainax also forced Anno to replace the planned ending of Evangelion with two episodes set in the main characters’ minds. In 1997, Gainax launched a project to re-adapt Evangelion’s scrapped ending into a feature-length film. Once again, budgeting issues left the film unfinished, and the completed 27 minutes of animation were included as the second act of Evangelion: Death and Rebirth. In response, Anno received several letters both of encouragement and criticism, including death threats and letters of disappointment from fans who thought Anno had ruined the series for them. Eventually, the project culminated in The End of Evangelion, a three-act film that served as a finale to Neon Genesis Evangelion.

In September 1999, Anno appeared on the NHK TV-documentary “Welcome Back for an Extracurricular Lesson, Senpai!”, answering some Evangelion-related questions, including the origin of the name Evangelion, and teaching children about animation production.

Also released in 2004 was the movie Funky Forest (ナイスの森, Nice no Mori), in which Anno makes several acting cameos: as the student in the front row of the “Home Room!” skit sitting next to Hataru, in “Who’s the Director?” as an animator who feels he is being overworked, and finally in “Singles Picnic” he is among the men awaiting females who never come.

On August 1, 2006, Hideaki Anno’s official website was updated with job listings for key animators and production staff at a company he founded, Studio Khara. In September 2006, it is reported by the October edition of the Japanese animation magazine Newtype. On September 9, 2006, GAINAX’s official website confirmed that Rebuild of Evangelion was in the works. The first three movies would be an alternate retelling of the TV series (including many new scenes, settings, backgrounds, characters), and the fourth movie would be a completely new conclusion to the story. Kazuya Tsurumaki and Masayuki would direct the movies while Yoshiyuki Sadamoto would provide character designs and Ikuto Yamashita would provide mechanical designs. Shinji Higuchi would provide storyboards for the first movie. The first was launched in Summer 2007, and the second and third were planned to be launched in 2008, however, the second installment was released by itself on June 27, 2009. The third movie was to be released simultaneously with the fourth, instead, the third movie was released on November 17, 2012 and the release date for the fourth movie in Japan was announced to be June 27, 2020. On February 17, 2007, Anno published an official statement on the Japanese Yahoo Portal for the films regarding his personal involvement and goals in their production.

In October 2007, Hideaki Anno resigned from Gainax. In 2011 Anno co-produced the Koinobori Pictures movie Kantoku Shikkaku (“Failed Director”), directed by Katsuyuki Hirano featuring Yumika Hayashi.

Anno has appeared in manga twice, both created by personal acquaintances. His wife, Moyoko Anno, wrote Insufficient Direction, a chronicle of their courtship and marriage and depicting Anno’s “true face” as “the founder of the otaku cult”. In 2007, a college-age version of him appeared alongside other Gainax founders Hiroyuki Yamaga, Takami Akai, and Toshio Okada in the Kazuhiko Shimamoto manga Aoi Honō. Anno attended Osaka University of Arts with Shimamoto. Aoi Honō was adapted into a live-action television drama in 2014, where Anno was played by actor Ken Yasuda. The 2014 animated series Shirobako has a walk-on appearance by a character named “Mitsuaki Kanno”, who is an obvious caricature of Anno.

In 2012, Anno was the curator of an exhibit entitled Tokusatsu- Special Effects Museum-Craftsmanship of Showa and Heisei Eras Seen Through Miniatures, held at the Museum of Contemporary Art Tokyo, featuring actual props and suits from many of Japan’s tokusatsu films and TV shows. Anno also produced a short live-action film for the exhibit, entitled A Giant Warrior Descends on Tokyo, featuring the Giant Warrior-God from Studio Ghibli’s animated film Nausicaä of the Valley of the Wind.

Anno has gone on to work with Hayao Miyazaki and Studio Ghibli on several short films which have been shown at the Ghibli Museum. He also voiced the main character Jiro Horikoshi in Miyazaki’s 2013 feature film The Wind Rises.

Anno designed the Space Battleship Yamato 2199 sci-fi anime television series opening sequence. In 2014, Anno and Studio Khara launched Japan Animator Expo, a series of original net animations made by various directors.

On April 15, 2015, Anno spoke about his feelings regarding Asuka and Rei. He claimed: “The truth is, I have no emotional attachment to Rei at all. In the midst of making Eva, I suddenly realized that I had forgotten her. Her very existence. For example, in episode seven, I remembered and added one shot with Rei. I had no attachment to her at all. I think that was okay, because in episode eight, she didn’t appear. Not even in a single shot.”

In March 2015, it was announced that Anno would team up with close friend and Gainax cofounder Shinji Higuchi to write and codirect Shin Godzilla, the 2016 reboot of Toho’s Godzilla franchise.