"Beelzebub" centers on Tatsumi Oga, a delinquent student at Ishiyama High, a school notorious for its violent and unruly environment. Oga's life takes a drastic turn when he encounters a man floating down a river, who splits open to reveal a baby named Kaiser de Emperana Beelzebub IV, the son of the Demon Lord. Oga is chosen as the caretaker of Beelzebub, tasked with raising him to become the future ruler of the demon world. The baby is accompanied by Hildegard, a demon maid who assists Oga in his new role.

As Oga navigates his responsibilities, he faces numerous challenges, including battles with other delinquents, supernatural entities, and rival demons. The series blends action, comedy, and supernatural elements, with Oga often finding himself in absurd and chaotic situations due to Beelzebub's unpredictable powers. Despite his tough exterior, Oga gradually forms a bond with the baby, showcasing a more compassionate side.

Key characters include Furuichi, Oga's best friend and frequent comedic foil, who often gets dragged into the chaos. Hilda, the stern and powerful demon maid, serves as a constant reminder of Oga's duties and often clashes with him over his caregiving methods. Aoi Kunieda, a skilled fighter and classmate, becomes a significant ally and love interest for Oga. The narrative also introduces various antagonists, such as the Tōhōshinki, a group of powerful delinquents, and other demons who seek to challenge Beelzebub's claim to the throne.

The story progresses through a series of episodic adventures and longer arcs, balancing humor with intense battles and character development. Oga's journey is marked by his growth from a carefree delinquent to a more responsible individual, shaped by his experiences with Beelzebub and the challenges they face together. The series concludes with Oga and his friends overcoming significant threats, solidifying their bonds and ensuring Beelzebub's safety as he continues to grow into his destined role.