Some 400,000,000 years after an advanced human civilization was destroyed by an alliance of planetary conquerers known as Warp Monarch, 12 direct descendants of the civilization's warriors (called Sazers) awaken their powers and join forces with the other members of one their ancestors' four tribes: Flame, Wind, Earth and Water. Each Sazer is based on a Zodiac sign represented in an animal totem or spirit representation. At first, they wage war on each other, but after learning the truth of their ancestry and their reason for awakening, the GranSazer tribes unite to protect Earth from the Warp Monarch from once again extinguishing all life on the planet.

The series revolves around three humans named Shouta Date, Yuka Sanada and Shinya Hiraga who one day find themselves as the new heroes of the planet Earth. Centuries ago, an alien from Azure Planet named Nolun was battling an evil lord named Kaiser Hades. After a long fight between good and evil, Nolun's army won and Kaiser Hades was sealed somewhere on Earth. After so many years, Kaiser Hades returnes with his partner named Dr. Zora. Both of them decide to conquer Earth and send monsters such as the Zakoal, Cyber Knights and his large monsters named the Space Beasts to attack Earth. Seeing this, Nolun gives part of her powers to Shouta, Yuka and Shinya so they can transform and become the Justirisers! Armed with special powers and the Genseishin and supported by Mio, Reika and many other humans, the Justirisers are on the mission to defeat Kaiser Hades and his army though hades and his minions are defeated his older brother majin daruga and his imperial army soon come to destroy the planet now they must work hard to defeat this powerful menace.

In the year 2500, the Earth has been taken over and covered in darkness by a race known as the Neo-Descal. The remaining members of the human resistance send their trump card weapons, the three Meteor God warships to the past to try to change the future by stopping Neo-Descal in 2005, when their attacks began. Along with the Meteor God warships comes Ad, captain of the Adle-Eagle squad and his right hand man, Gordo, Kane, captain of the Beet-Vizor squad, and the twin Sazers Ein and Zwein, and Remy, who pilots Great Lio. Ad and Kane are joined by Takuto Andou, whose grandfather met Captain Shark, leader of the resistance, as a young man and was left with a Knuckle Cross to allow his grandson in 2005 to become the third member of the team known as Sazer X. Sazer X fight the space pirates known as Descal, and later Neo-Descal when they arrive from the future after the defeat of their ancestors. Captain Shark, known as the Shark Sazer, arrives later from the future, along with his rival, Jackall, a mysterious Sazer-like being who holds one of Shark's greatest secrets.