The story is told mostly in flashback, after being framed with a scene from the present wherein Kratos, standing atop the tallest cliff in Greece, laments how the gods have abandoned him and tosses himself into the waters below.

While the player starts the game three weeks prior to this event, Kratos' background is told by the Narrator during the game (revealed to be the Titan Gaia in God of War II). Kratos was a fearsome Spartan warrior, and grew his fifty-man squad into an army of thousands via strategy, tactics, ferocity and conquest. However, in a battle against a barbarian horde, his army was massacred, and, in a desperate measure, Kratos offered his life and service to Ares, the God of War, in exchange for Ares defeating the Barbarians. Ares, sensing enormous power in Kratos, accepted his offer and destroyed the Barbarians. He also granted Kratos the Blades of Chaos, curved blades forged in the pits of Hades that were attached to long chains which were fused to Kratos' arms.

Kratos then became Ares' servant, leading his Spartan army in conquering much of Greece. In one battle, they came across a village that worshiped Athena and put the residents to the sword, and their homes to the flame. There, Ares put Kratos into a blood lust driven rage and it made him kill anyone standing in his way. Despite his own foreboding feelings and the warnings of the local oracle, Kratos entered the village's temple and slaughtered all within. Unfortunately, after his blood-lust cleared, he realized that his two last victims had been his own wife and daughter; Ares explained that this village had been a test of Kratos' power, severing the last of his humanity. The village Oracle cursed Kratos, binding the ashes of his dead family to his skin; this new pale coating gave rise to Kratos' new title, "the Ghost of Sparta." and it made everyone in Greece fear him. Kratos renounced his service to Ares and began to wander the Earth, lamenting his deeds, while serving the other gods of Olympus for ten years.

The player becomes involved in Kratos' story as he is approaching Athena's city, Athens, under siege by Ares' army. While in the Aegean Sea, Kratos's ship is attacked by Ares's forces. After impaling the massive heads of the fearsome Hydra, Kratos is approached by Athena, who wants him to stop Ares and save her city. Kratos agrees on one condition; that the gods relieve him of the nightmarish memories of his past crimes, as well as allowing him a chance at redemption. Kratos fights his way through the attacking forces to find the Oracle of Athens, and learns from her that only Pandora's Box can give a mortal the power to kill a god. Unfortunately, due to the gods' fear of this power, the box is locked deep within Pandora's Temple, constructed on the back of the Titan Cronos, whom Zeus cursed to wander the Desert of Lost Souls until the sands rip the flesh from his bones.

Kratos makes his way to the Temple, defeating many foes and evading the many traps built into the Temple by its crazed architect, Pathos Verdes III. He recovers Pandora's Box, but Ares senses his success, and throws a pillar from Athens to the Temple, impaling Kratos on a wall and killing him. As Kratos was pinned to the wall dying, Ares steals Pandora's box and Kratos is sent to the Underworld. However, Kratos is able to escape the Underworld with help from a mysterious grave digger, who refers to Kratos as "my child". He returns to Athens, regains Pandora's Box, and confronts Ares.

When Kratos proves that he isn't just a mortal after all, Ares makes a desperate attempt to drive Kratos mad by making him relive the death of his family. Opening a portal, Ares traps Kratos in an illusion. Ares recreates the temple where Kratos slew his wife and child, along with images of Kratos's Family. Ares then creates copies of Kratos which attack his wife and child. After this fails, Ares strips the Blades of Chaos from Kratos' arms, taking back the weapons he had given him, and impales Kratos' family with them with Kratos watching in horror. Freed from his own mind but without weaponry, Kratos is at the mercy of Ares until he spots a very large metal sword, which was formerly used as an ornamental bridge inside Athens. With it, he engages, defeats and kills his former master, the God of War.

After receiving the congratulations from the gods, Kratos asks Athena to remove the nightmares of his past. Athena explains that the gods can only forgive him for his sins; the nightmares, unfortunately, are permanent. Feeling abandoned by the gods, Kratos climbs back to the bluffs overlooking the Aegean Sea and, as the game comes full circle, tosses himself over the edge. However, as he breaks the waves below, he is pulled out by Athena. He has served the gods well, she explains, and there is a throne waiting for him that currently has no occupant: the throne of the God of War.