The anime is based on the manga of the same name by Yuki Midorikawa, and has been produced across multiple formats since 2008, including seven TV seasons, OVAs, and theatrical films.

At the 3rd Seiyu Awards, Hiroshi Kamiya won Best Lead Actor for voicing Takashi Natsume and Kazuhiko Inoue won Best Supporting Actor for voicing Nyanko-sensei.

According to an anime expert familiar with Chinese otaku culture, the series is considered a pioneering work that started the trend of Japanese yokai/supernatural-themed anime becoming popular in China, and it uniquely attracts fans across a wide range of age groups there.

For the OVA 'Itsuka Yuki no Hi ni', two audio dramas titled 'Itsuwari Kami' and 'Mamori Inu' were written specifically for the SOUND THEATRE project by playwright Bun'ou Fujisawa.

Starting with the fifth season in 2016, the animation production studio changed to Shuka.

For the second theatrical film, the episode 'Ishiokoshi' was chosen partly because a producer remarked that the character Mitsumi was 'cute', which led the production team to settle on this standard Natsume-solves-a-yokai-problem story.

Director Hideki Ito deliberately toned down how adorably Mitsumi was portrayed in 'Ishiokoshi', worried that making her too cute would make the story feel like bullying and change the audience's perception of the whole narrative.

Kumamoto Prefecture's Hitoyoshi city and the Kuma region collaborated with the anime starting in 2011, including promotional posters, a sightseeing map of locations featured in the anime, and Nyanko-sensei being used as a PR character for the Hitoyoshi fireworks festival; the region was later selected in the 2025 edition of the 'Anime Pilgrimage 88' list by the Anime Tourism Association.