The story unfolds on post-apocalyptic earth, 700 years after a meteorite collision nearly wiped out all human civilization. Out of the ashes, the Immortals united and swore an oath to abandon the Game and preserve the knowledge that humanity had lost. But one immortal, Kortan, did not swear the oath - he still sought the prize and his empire grew until he controlled most of the planet from his fortress Mogonda. Connor MacLeod (the protagonist of the original film) challenged Kortan and was defeated (as any immortal who broke the oath was destined to die).

With Connor's death came the prophecy of the rise of a new immortal, he would defeat Kortan. Ramírez, now a Jettator, has since waited seven hundred years for the unavowed immortal.

Quentin MacLeod leads the resistance against Kortan, with Ramírez as his mentor he seeks the Jettators (those who took the oath) to gain their Quickening and their knowledge - not by beheading but by a sharing as MacLeod and Jettator grasp the same sword simultaneously (although it is sometimes called a quickening, and the effects are sometimes just as destructive to the surrounding area). In the wake of a sharing the Jettator becomes mortal and often his sword shatters to signify this.

With the wisdom of Ramírez and the Quickenings of the Jettators, he may be able to destroy Kortan. Some episodes involved Jettators making use of a loophole in their oath to challenge Kortan regardless, such as Matsuda, who built a cyborg to fight Kortan in his stead, or Cornell, who changed his name to Orion to be able to fight Kortan.

Despite being redesigned to attract a younger audience, the show was surprisingly mature/violent; it wasn't uncommon for minor characters to die, and while Quentin had found a way to take another Immortal's power and knowledge without also taking their life, Kortan still did it the old way, by beheading them. Though essentially a good-versus-evil scenario, most of the characters on both sides were more than just black and white heroes and villains.

Many of Kortan's henchmen are shown to have good characteristics and feelings - and even on occasion Quentin will be tempted by greed and be selfish, especially when offered the chances of immense power. Of course, ultimately, his good side always wins through.