In "I've Been Killing Slimes for 300 Years and Maxed Out My Level," Azusa Aizawa, an overworked office worker in modern-day Japan, dies from exhaustion and is reincarnated in a fantasy world as an immortal witch. Seeking a peaceful life, she settles in the countryside and spends her days killing low-level slimes for modest income, avoiding conflict and danger. Over the course of 300 years, her repetitive slime-killing inadvertently maxes out her level, making her one of the most powerful beings in the world.

Azusa's quiet life is disrupted when her immense power attracts attention. A dragon named Laika challenges her to a duel, but after being defeated, Laika becomes her apprentice and moves in with her. This marks the beginning of Azusa's gradual accumulation of companions, including Falfa and Shalsha, two slime spirits who adopt her as their mother; Halkara, a clumsy elf who runs a potion business; and Beelzebub, a demon king who becomes a close friend. Despite her overwhelming strength, Azusa remains committed to her simple, peaceful lifestyle, often using her power to help others or resolve misunderstandings.

The series explores Azusa's interactions with her growing circle of friends and neighbors, blending slice-of-life elements with light fantasy adventures. Episodes often focus on mundane yet heartwarming activities, such as running errands, hosting visitors, or solving minor problems in the community. While occasional threats or challenges arise, the tone remains lighthearted, emphasizing camaraderie and the joys of a relaxed life. Azusa's journey is less about grand battles or world-saving quests and more about finding fulfillment in the small, everyday moments shared with her newfound family.