In a world overtaken by war and conflict, "Hypnosis Microphones"—devices through which a user channels lyrics that can affect the listener's brain and even cause physical damage—were introduced to the masses by the Party of Words. Revolutionizing warfare, Hypnosis Mics have transformed words and music into the sole weapons used by gangsters, terrorists, and the military, with physical weapons having been banned from use. As a result of swooping in during the chaos, the all-female Party of Words rules over the Japanese government. Women in Japan now live in Chuuouku, while men battle over surrounding territories outside the ward through rap battles. With intentions unknown, the Party of Words begins to gather the former members of the now-disbanded legendary rap crew The Dirty Dawg to fight not for territory or war, but for their respective crew's pride and honor in the greatest rap battle of all time. The first Division Rap Battle is about to commence, and practice is not something these rappers are going to need.

Otaku siblings Tamotsu and Niwaka Denkigai are shopping in Akihabara when it is overrun by vampiric cosplaying monsters! These creatures, known as "Bugged Ones," can possess anyone they bite and soon they begin causing mayhem across the city. As Tamotsu finds himself at the mercy of one of these creatures, he is rescued by the mysterious baseball bat-wielding Matome Mayonaka. Together, they fight through several more encounters with the Bugged Ones, but before long, Tamotsu is fatally wounded protecting Matome. With no other choice, she revives him as a high level Bugged One—just like her! Tamotsu and Matome, along with excitable otaku cosplayer Arisa Ahokainen, make up the group "The Electric Mayonnaise" and they begin dispatching the Bugged Ones in the only way they know how: by ripping off their clothes and exposing them to sunlight!

A recent uptick in civilian riots and crimes has been observed across the country following the conclusion of the second Division Rap Battle. To make matters more chaotic, the individuals perpetrating the crimes have no recollection of the incidents nor any reason to be committing them in the first place. Suspecting these events to be linked to the effect of the Hypnosis Microphones, the governing Party of Words begins investigating the whereabouts of the mastermind behind them. These cases have been more frequent in the six divisions, and their respective leaders are scrambling to find a way to prevent further havoc. But when the culprit pulling the strings threatens their territories with more calamity, the six leaders must put aside their personal differences and work together to stop this mayhem.

Dreaming of becoming a top-tier professional in the fast-paced, competitive world of voice acting, rookie Futaba Ichinose frantically scurries around, searching for auditions and performance sessions. Rubbing elbows with some of the biggest names in the industry, she tries to find her own unique voice and style. Along the way, she befriends two important allies: Ichigo Moesaki, an aspiring idol who claims to be a princess from another planet, and Rin Kohana, a cheerful child actress who tries her best to balance her career and school at the same time. Together, the girls brave the ups and downs of the entertainment industry—but as for Futaba, whose performance assessment at her agency is just around the corner, her career might be over sooner than expected! Sore ga Seiyuu! is a humorous and sincere celebration of the industry that gives anime its voice.