Cyborg 009, created in 1963, became the first superpowered hero team created in Japan. That same year, Kazumasa Hirai and Jiro Kuwata created Japan's first cyborg superhero, 8 Man (which predated Kamen Rider by eight years). The success of the tokusatsu superhero TV series Kamen Rider, produced by Toei Company Ltd. in 1971, led to the birth of the "Transforming" (henshin) superhero (human-sized superheroes who transform by doing a pose, and use martial arts to fight henchmen and the weekly monster), and resulted in many sequel shows to this day. Ishinomori then created many similar superhero dramas, which were once again all produced by Toei or in Sarutobi Ecchan's case Toei Animation, including Android Kikaider , Henshin Ninja Arashi, Inazuman, Robotto Keiji, Secret Task Force Goranger (the first Super Sentai series), Kaiketsu Zubat, Akumaizer 3, Sarutobi Ecchan, the Toei Fushigi Comedy Series and countless others. He even created popular children's shows such as Hoshi no Ko Chobin (Chobin, Child of the Stars, 1974, a co-production with Studio Zero which was a major success on Italian television), and Ganbare!! Robokon.

Ishinomori's art is quite reminiscent of that of his mentor, Osamu Tezuka. The true story of his first meeting with Tezuka was illustrated in a short four-page tale drawn up as supplementary material for the 1970s Astro Boy manga reprints. Around 1955, Ishinomori submitted work to a contest seeking new talent in the magazine, Manga Shonen. Tezuka was impressed by his drawings and asked Ishinomori to help him with Astro Boy. In the American release, this story can be seen in Volume 15, along with Ishinomori's earliest work on the "Electro" story arc.

Ishinomori also illustrated a comic adaptation of the Super NES video game A Link to the Past, which was produced for the American publication Nintendo Power. The comic consisted of 12 chapters, which were serialized from January 1992 (Volume 32) to December 1992 (Volume 43). The comic was republished as a graphic novel collection in 1993.

At the end of 1997, Kazuhiko Shimamoto, a young and up and coming mangaka was contacted by an increasingly ill Shotaro Ishinomori and asked if he would do a continuation (though more along the lines of a remake) of his 100-page, one-shot manga from 1970, Skull Man (the manga that became the basis for Kamen Rider). Ishinomori, who had been one of Shimamoto's boyhood heroes, faxed him copies of the proposed story and plot notes. Shimamoto was astounded that he had been chosen to work on his idol's final, great work.

Shimamoto had already been involved in the revival of one of Ishinomori's other earlier works (including Kamen Rider) but little did he dream that, as only one of many whom Ishinomori had inspired, he would be chosen for the final collaboration and resurrection of Skull Man. It was also recently adapted into an anime in 2007.

Ishinomori died of heart failure on January 28, 1998 just 3 days after his 60th birthday. His final work was the tokusatsu superhero TV series, Voicelugger, televised a year later. Two years later, the Kamen Rider Series would be revived with Kamen Rider Kuuga. All of the series made in the Heisei period credit Ishinomori as the creator. The Ishinomori Manga Museum named in his honor opened in Ishinomaki, Miyagi in 2001. Special trains in the Senseki Line were commissioned featuring his artwork generally leading to the museum.

His work posthumously awarded him the Guinness World Record for most comics published by one author, totaling over 128,000 pages.