Twins Megumu Kobayashi and Mitsuru Kobayashi attend different schools, one for girls and one for boys. One day, bored with being surrounded by others of their own gender, they decide to swap places with one another. While the deception seems to go unnoticed for some time, things get a bit more complicated when the possibility of romance arises.

Kobayashi ga Kawai sugite Tsurai!! begins when a heartfelt confession from Megumu leads to sharing a kiss with the upperclassman Aoi Sanada while disguised as her brother. This leaves Aoi, who was never good with girls to begin with, questioning if he likes guys instead. Likewise, Mitsuru finds the haughty queen of the school, Azusa Tokugawa, in a vulnerable position that leaves her heart racing while in his (her) arms. The two couples are lovey-dovey, but the secret of the twins' switched identities has not been revealed yet...