Some 400 million years ago, an advanced human civilization was nearly wiped from the face of the Earth by the Warp Monarch, a powerful alliance of alien races. In the present day, the lost technology of that ancient society begins to stir, awakening the dormant DNA of twelve chosen descendants. These individuals become the Gransazers, warriors marked by a glowing zodiac symbol on their left hand who can transform into armored fighters using a device called the Knuckle-Riser. The twelve are divided into four elemental tribes of three: the bird-themed Flame Tribe, the insect-themed Wind Tribe, the land mammal-themed Earth Tribe, and the aquatic-themed Water Tribe. Each tribe is capable of summoning a giant transforming mecha known as an Ultra Star God to battle equally colossal threats.

The story begins with the tribes at odds, having been deceived into fighting one another, particularly the Wind Tribe who are manipulated by an alien impostor. The central protagonist is Tenma Kudou, a hot-headed motorcycle courier who transforms into Sazer Tarious of the Flame Tribe. He is joined by Mika Shidou, a skilled martial artist and lab assistant who becomes Sazer Mithras, and her younger brother Ken, the compassionate Sazer Lion. As the initial conflicts subside and the truth about their shared ancestry is revealed, the twelve warriors must learn to unite against the true enemy, the Warp Monarch. This cosmic alliance includes the Akelon, a race of humanoid aliens, and later more formidable forces such as the robotic Impactors and the ancient, energy-draining Bosquito.

As the series progresses, the narrative follows the Gransazers as they move from infighting to cooperation. The Earth Tribe, led by the stoic former boxer Naoto as Sazer Tawlon, and the Water Tribe, led by the observant reporter Makoto as Sazer Gorbion, eventually join forces with the Flame and Wind tribes. A significant arc involves Ran Saotome, Sazer Visuel of the Earth Tribe, who is revealed to be the Communicator, a unique Gransazer with the ability to interface with ancient records and the cosmic will itself. The heroes face a series of alien envoys sent by the Warp Monarch, including the manipulative Karin and the powerful Logia. After many battles and the loss of their Ultra Star Gods, the Gransazers achieve a final victory against the Warp Monarch’s will, proving humanity’s right to exist. With the threat ended, the ancient mecha depart from Earth, and the twelve warriors return to their normal lives.