Earth's once green hills and rich blue oceans have been converted into a desolate wasteland by the relentless onslaught of planet bombs from the expansionist Gamilas Empire. By the year 2199, humankind has retreated to the depths of underground cities to escape the radiation.

However, all hope is not lost, as the distant planet Iscandar offers Earth its final salvation: the Cosmo Reverse System, capable of restoring Earth's irradiated surface. In a desperate bid to retrieve this technology from Iscandar, the Earth Defense Force pours its remaining resources into the Yamato—an innovative, state-of-the-art battleship equipped with an infinite energy Wave Motion Engine.

From young talent such as Tactical Officer Susumu Kodai to accomplished veterans like Captain Juuzou Okita, the Yamato's crew consists of many individuals, all varying in their experience on the battlefield. But despite their differences, one goal unifies them all: to complete their perilous 168,000 light-year voyage to Iscandar and save humanity from imminent doom.