Third-year college student Shinichi Sakurai simply wants to spend his days in peace. Instead, he ends up spending most of his time with his lively and well-endowed junior, Hana Uzaki.

Worried that her gloomy-faced senior will spend his college years all alone like he did during high school, Uzaki takes it upon herself to fill Sakurai's days with excitement, constantly dragging him around to hang out with her. Through their shared experiences, the spirited Uzaki shows her reclusive senior that spending time with friends can be worthwhile. And although Sakurai finds Uzaki's endless teasing to be a great annoyance, he continues to enjoy the days they spend together—many ending in some hilariously misleading situations.

Uzaki-chan wa Asobitai! is a slice-of-life story following the comedic antics of Sakurai and Uzaki who, despite having polar opposite personalities, develop an odd but charming relationship.