Minato Sahashi has failed the college entrance exam twice, is awkward around women, and unemployed. Growing up, Minato could never stand up to his mother or little sister, a trend that continues to this day. In reality, Minato is extremely intelligent, yet his inability to cope under pressure results in his constant failure. As a result he has been branded an idiot and loser by many.

One day, Minato meets a girl named Musubi, who literally falls from the sky. Musubi, who is under attack, runs off with Minato in tow. Minato soon learns that he is an 'Ashikabi', humans with specific genetic traits that allows them to partner with 'Sekirei'. The Sekirei are 108 super-powered beings created by the mysterious MBI corporation. Made up of cute girls, buxom women, and bishōnen, the Sekirei fight in a dangerous and sometimes deadly competition called the 'Sekirei Game'.

With the entire city of Tokyo as the battlefield, the Sekirei seek out those humans who are destined to become their Ashikabi partner. Minato soon learns that being the partner of a beautiful girl is not all fun and games, especially when he discovers that an Ashikabi can have more than one Sekirei partner, and that's where the real trouble starts.