Nozomu Itoshiki is a high school teacher so pessimistic that even the smallest of misfortunes can send him into a pit of raging despair; some of these "catastrophes" even lead to suicide attempts. Sayonara Zetsubou Sensei is a satirical slice-of-life comedy set in the modern day, covering various aspects of Japanese life and culture through Nozomu and his interactions with his students: Kiri Komori, a recluse who refuses to leave the school; Abiru Kobushi, an enigma who frequently arrives to class with severe and mysterious injuries; the hyper-optimistic Kafuuka Fuura, Nozomu's polar opposite; and several other unusual girls, all of whom are just as eccentric as their teacher.

Media Blasters initially held the license to Sayonara Zetsubou Sensei, but dropped it in 2010 without any DVD/Blu-ray release. It remained unlicensed until Anime Expo 2019 when Nozomi Entertainment announced they had licensed the series.