Tetsuya Takeda is back for his sixth season as Japan's most dedicated middle school teacher. Sakura Middle School becomes the first school to introduce the new student-guidance standards set to be instituted by the education ministry next April. Two transfer students also will join the 3B class and, in a historic first, the school will have a non-Japanese teacher on staff.

3年B組にやって来た二人の転入生、直と政則が新たな波紋を投げかける。直は性同一性障害だったのだ。そして、桜中学の校長に金八と正反対の教育哲学を持つ人物が赴任。さらに、坂本家では長男・幸作の身に病魔が…。教室・職員室・家庭、それぞれで起こった“三重苦”に金八先生はどう立ち向かうのか？