"Goku Sayonara Zetsubō Sensei" is a surreal and satirical anime series that revolves around Nozomu Itoshiki, a high school teacher who is perpetually consumed by despair. Nozomu, whose name can be written with characters meaning "despair," frequently contemplates suicide and views the world through an overwhelmingly pessimistic lens. Despite his bleak outlook, he is tasked with teaching a class of eccentric and unconventional students, each embodying various societal quirks and absurdities. The series is structured as a series of vignettes, blending dark humor, social commentary, and absurdist comedy.

The students in Nozomu's class are caricatures of modern Japanese societal trends and behaviors. Among them is Kafuka Fuura, an overly optimistic girl who interprets every situation in an absurdly positive light, often clashing with Nozomu's despair. Other notable students include Chiri Kitsu, a perfectionist with obsessive-compulsive tendencies; Abiru Kobushi, a girl who constantly wears a paper bag over her head due to her insecurities; and Meru Otonashi, a quiet and emotionless girl who rarely speaks. Each character represents exaggerated traits or societal issues, creating a dynamic and often chaotic classroom environment.

The narrative lacks a traditional linear plot, instead focusing on episodic explorations of themes such as existentialism, nihilism, and the absurdities of modern life. Nozomu frequently delivers monologues on the futility of existence, often punctuated by his signature catchphrase, "Zetsubō shita!" ("I'm in despair!"). These moments are juxtaposed with the students' bizarre antics and interactions, creating a tonal balance between dark humor and philosophical musings. The series also incorporates meta-commentary on anime tropes, pop culture, and societal norms, often breaking the fourth wall or employing surreal visual gags.

Throughout the series, Nozomu's interactions with his students and the world around him highlight the contrast between his despair and their often misguided attempts to find meaning or happiness. The show's humor derives from its exaggerated characters, rapid-fire dialogue, and satirical take on contemporary issues. Despite its comedic tone, the series frequently delves into darker themes, exploring the tension between hope and despair, individuality and conformity, and the absurdity of human existence.

"Goku Sayonara Zetsubō Sensei" is characterized by its unique visual style, featuring minimalist backgrounds, exaggerated character designs, and frequent use of text overlays and visual puns. The series' unconventional storytelling and thematic depth make it a distinctive entry in the anime medium, blending comedy and existential reflection in a way that challenges conventional narrative structures.