Guts (ガッツ, Gattsu?) is a wandering mercenary who is taken in by the mercenary group the "Band of the Hawk" (鷹の団, Taka no Dan?) after being swiftly defeated by its leader Griffith, and soon becomes his right-hand man while making a name as the group's renowned raid leader. Shortly afterwards during an encounter with a monstrous man known as Nosferatu Zodd who defeats both Guts and Griffith, Zodd notices the Crimson Behelit in Griffith's possession; a trinket in the shape of a face, and leaves promptly, warning Guts that his continued friendship with Griffith will result in his death.

The Hawks play a pivotal role in ending the 100-year war that has ravaged the country of Midland and are initially welcomed as heroes, but Griffith's aspirations to rule his own kingdom are shattered when Guts leaves the Hawks to find his own dream. Unable to cope with the loss, Griffith seduces the King's daughter Charlotte but is caught and ends up in the dungeon for a year. By the time Guts learns of this and helps the outlawed remnants of the Hawks rescue him, Griffith has been horribly mutilated and rendered a mute shadow of his former self.

The weight of knowing his body is too damaged for him to fulfill his dream proves too much for Griffith and he accidentally activates the Crimson Behelit on his person. This brings the Hawks to another plane where they encounter archdemons known as the God Hand in a ceremony known as "the Eclipse". Urged onward by the eldritch beings, Griffith sacrifices his soldiers to the God Hand's "apostles" — humans like Zodd who sacrificed their loved ones and humanity for power — so that he can become the God Hand's fifth and final member, taking the name Femto.

Branded, Guts witnesses the brutal slaughter of his comrades, though he and his lover Casca are saved from certain death by the mysterious Skull Knight. Guts loses an arm and an eye while Casca is driven insane after being raped by the reborn Griffith. Leaving Casca in the care of Rickert, a survivor of the Band of the Hawk who was not spirited into the other plane, and the blacksmith Godo, Guts begins hunting down the apostles in search of revenge against Griffith, although his Brand of Sacrifice makes him a target for restless spirits that hunt him nightly.

Years after beginning his journey, Guts is joined by the elf Puck whose company he eventually accepts. Guts is later reunited with Casca as she is about to be burned as a witch in the city of St. Albion. There, encountering Farnese of the Holy See Church's Holy Iron Chain Knights, Guts endures a nightmarish ordeal that ends in Griffith's physical form restored. As Guts takes Casca to the Elven realm of Elfhelm for sanctuary with the help of his new companions, Griffith creates a second Band of the Hawk with Zodd and other Apostles among its ranks to battle the invading Kushan army. The war between Griffith and the Kushan emperor, a rogue apostle, climaxes with the emperor's destruction and the overlapping of the mortal realm and the supernatural. No longer challenged by demon or man, Griffith establishes his rule over Midland with the endorsement of the Pope and Princess Charlotte, creating the city of Falconia to provide the Midlanders with refuge from the ever-increasing attacks of mythical beasts, unaware their new ruler is actually one of them.