"AKB0048" is set in a futuristic universe where entertainment and performing arts are banned by authoritarian governments, deemed as threats to societal order. In this world, the legendary idol group AKB0048 emerges as a symbol of rebellion, using their music and performances to inspire hope and resistance. The group operates as a guerrilla unit, traveling across galaxies to stage illegal concerts, often facing opposition from the Dess forces, a military organization tasked with enforcing the entertainment ban.

The story centers on a group of young girls who aspire to become successors of AKB0048, known as "successor candidates." These candidates undergo rigorous training to inherit the names and roles of the original AKB48 members, such as Atsuko Maeda, Yuko Oshima, and Mayu Watanabe. The protagonist, Nagisa Motomiya, is a passionate fan of AKB0048 who dreams of becoming an idol. Alongside her friends, including the determined Chieri Sono and the reserved Orine Aida, Nagisa joins the successor program, navigating challenges such as intense training, rivalries, and the constant threat of Dess attacks.

As the series progresses, the girls uncover the deeper significance of AKB0048's mission. The group is not merely about entertainment but also serves as a beacon of hope and freedom, challenging oppressive regimes through their art. The narrative explores themes of perseverance, identity, and the transformative power of music, as the characters grow both as individuals and as performers. Key plot points include the discovery of the "Kirara," a mysterious energy source tied to the idols' performances, and the revelation of AKB0048's connection to the original AKB48 group from Earth.

The series features a mix of slice-of-life moments, action sequences, and musical performances, blending science fiction with idol culture. The characters' struggles and triumphs are interwoven with their journey to master their craft and uphold the legacy of AKB0048. By the end of the series, the successor candidates face pivotal decisions about their futures, balancing their personal aspirations with the greater mission of spreading hope through their music.