Hellsing originated from a one-shot titled 'Hellsing: The Legends of Vampire Hunter' published in 1996 in the hentai magazine Comic Kairakuten; Hirano stated he never intended to make an erotic story but rather a 'somewhat daring' action narrative, and his work in hentai simply facilitated the one-shot's quick publication.

After developing the one-shot into a full series, Hirano kept the setting but removed the erotic elements to focus on action, and due to the unconventional premise, he and publisher Shōnen Gahōsha initially tested reader reception before greenlighting full serialization.

Hirano wanted to build the story around gunplay but felt a traditional vampire didn't fit with firearms, so he redesigned Alucard with a hat and long coat to make him 'dark and ominous, but more suited to his behavior.'

Hirano noted that Alucard's design drew comparisons to Vash the Stampede from Trigun (which also ran in Young King OURs), which led him to regret giving Alucard sunglasses.

To balance out the series' dark tone, Hirano introduced Seras Victoria as a character meant to bring warmth and stand out 'from the darkness.'

The character Alucard's name is simply 'Dracula' spelled backwards, and Integra is said to be a descendant of Abraham Van Helsing from Bram Stoker's novel, even though the professor's name is actually spelled 'Helsing' without a 't'.

Hirano stated he did not do formal research for the series' many references to history, mythology, and pop culture, describing himself simply as an otaku who incorporated elements from media he passionately consumed.

The character Enrico Maxwell's appearance was modeled on actor John Robinson, while the Major's design was inspired by an antagonist from Hirano's earlier work 'COYOTE' and, according to the author, modeled after actor Philip Seymour Hoffman.

The character Heinkel Wolfe was originally a clearly female character in the prototype short story Crossfire, but in the main Hellsing series she is depicted as gender-ambiguous; official guidebooks describe her as 'futanari,' and the anime staff initially assumed the character was male, having originally planned to cast voice actor Tomokazu Sugita for the role.

For the OVA adaptation Hellsing Ultimate, producer Yasuyuki Ueda chose the original video animation format instead of a TV series specifically to avoid broadcast time constraints and to allow a more faithful, creatively unrestricted adaptation of the manga.

The Hellsing Ultimate OVA combined CG with traditional animation to realistically depict weapons and gunfire, a time-consuming process that was only feasible because the OVA release schedule was more flexible than a TV series.

Production of the Hellsing Ultimate OVA changed animation studios and directors multiple times over its run: Satelight handled episodes 1-4, Madhouse took over for episodes 5-7, and Graphinica finished the 'Final season' with episodes 8-10, with directors changing at each transition.

Manga creator Kouta Hirano publicly expressed dissatisfaction with the 2001 Gonzo TV anime adaptation and its staff on his own website, and in another of his works even included a line joking that he sold his Gonzo Hellsing DVDs to a used bookstore.

In a 2020 popularity poll by the anime news site Anime! Anime! about voice actor Jouji Nakata's roles, Alucard ranked second, with voters praising how well Nakata's voice matched the character and his skill in voicing Alucard's many different forms.

In a 2018 Anime! Anime! poll ranking the best anime speech scenes, the Major's pre-battle speech tied for first place with a scene from No Game No Life, with many voters specifically praising voice actor Nobuo Tobita's performance.

The Valentine brothers, minor early antagonists, became fan favorites and starred in recurring gag omake comics throughout the volumes; in the final volume's bonus pages, Hirano jokingly stated that the biggest event during Hellsing's serialization was not the OVA adaptation or the series' completion, but 'the existence of these two guys themselves.'