Noda Megumi, AKA Nodame, is a sloppy third-year Piano student at Momogaoka School of Music who lives and plays with abandon. Meanwhile, Chiaki Shin'ichi, an aspiring conductor, is at the top of his game, and acts the part. He notices something special in the way she plays Beethoven's Pathetique.

Chiaki is desperate to transfer from Piano to Conducting, but infamous conductor Franz Stresemann refuses to let him. Meanwhile, Stresemann recruits a band of misfits and flunkers to create Orchestra S out of misfits and near-dropouts, including Chiaki and Nodame's new mutual friends, Mine Ryutaro and Okuyama Masumi.

Chiaki turns out to be impossible to please. Nodame's terrestrial alien army invades Chiaki's apartment in an unidentified heating object, in a desperate attempt to reprogram him in time for the regular concert.

Maestro Stresemann's rightful owners arrive in Japan to take him home, while Orchestra S and Orchestra A prepare for the school festival concerts.

Nodame is desperately practicing the Rach 2, for reasons unknown. Orchestra S, meanwhile, is about to disband, just as they learn that Chiaki and the orchestra have become famous.

Chiaki and Orchestra A concertmaster Miki Kiyora recruit elite students from all over Japan to start a new orchestra. Nodame gets assigned to a new teacher, leading to her becoming a zombie.

Nodame contemplates attempting to treat Chiaki's fear of airplanes, which could lead to her losing him to Europe. Meanwhile, her teacher nominates her for the Maradona Piano Competition.

Brainwashed by Nodame, Chiaki goes on a plane trip to Hokkaido. Nodame prepares desperately for her competition, which could open the door for her to study in Europe.

Nodame loses herself at the Maradona competition, putting her Europe plan into doubt. Rising Star Orchestra, meanwhile, undergoes painful evolution.

Defeated, Nodame runs home to her parents' place in the countryside. Chiaki goes after her.