In 1945, World War II was abruptly ended when an alien race appeared on Earth and began to slaughter the human population. This alien force, known as the "Phantom Beasts" (or Genjyu in Japanese) had effectively taken over more than half of the Earth. The year is 1999 – 54 years later, mankind is still fighting to survive against the alien forces. Earth forces now use advanced mecha called Humanoid Walking Tanks (HWTs) to combat the invaders, but throughout the ordeal, far too many pilots have been killed in action.

To ensure the future of the human race, the Japanese government enforced a student draft which recruited high school students to become HWT pilots. Gunparade March follows the lives of the 5121st Platoon, which consists mainly of drafted high school students and their struggle to defeat the Phantom Beasts and at the same time, lead a normal social life. They are young people such as Atsushi Hayami and his high school class, also known as Unit 5121. This new generation fearlessly struggles on with the aid of the HWT humanoid combat machines and the devastating PBE bomb.