The game tells the story of Geralt of Rivia, who at the opening of the game is tasked to cure the daughter of King Foltest of a curse which causes her to transform into a feral monster. Geralt successfully cures her, introducing the player to the nature of witcher-work. A period of years mysteriously passes, ending with Geralt being transported to the witcher stronghold of Kaer Morhen by fellow witchers who had discovered him unconscious in a field. Geralt remembers almost nothing of his life before returning to Kaer Morhen.
The story begins with a large cutscene. It shows how Foltest, king of Temeria, hires Geralt to cure his daughter Adda from a curse in return for a night with her. Geralt captures the traitor who cast the curse and uses him as bait to attract the striga (the monster Adda turns into). A battle ensues and Geralt scares the striga away with magic. Geralt then goes into the sarcophagus where she sleeps and shuts her out. The next morning, he finds her as a human.
The prologue begins, where Geralt is found by his fellow witchers. At the end of the witcher series Geralt was killed, but somehow he was revived, but now has amnesia. He is taken to Kaer Morhen, the base of the witchers, where he meets a sorceress named Triss Merigold. The castle is attacked by a gang of bandits named Salamandra, led by a criminal known as the Professor, a mage named Savolla who controls a large, praying mantis like monster, and another mage named Azar Javed.The witchers and the sorceress manage to slay the monster, kill Savolla, but the Professor and Azar manage to escape with the mutagens that genetically alter the witchers.
After curing Triss of the wounds she received while fighting Javed and then romancing her, Geralt and the rest of the witchers head off in different directions in order to find information on Salamandra. Geralt heads south to Vizima, capital of Temeria and where king Foltest reigns. He goes to the outskirts, where he meets a powerful child and an old friend, Shani, whom he does not remember. He finds out that Vizima is in quarantine. But, by doing favors to some important officials, either saving or condemning a witch, uncovering a conspiracy between Salamandra and those officials, either sparing or slaying most of the town, and killing a giant ghost-like hound, he gets a pass and prepares to enter Vizima just to be arrested.
He awakes in a jail where he volunteers to kill a cockatrice in the sewers in exchange for his freedom. In the sewers he meets a knight of a monster-slaying order, the Order of the Flaming Rose, names Siegfried, who not only helps him kill the monster but also directs him to a private eye who can help Geralt defeat Salamandra. Geralt spends the rest of part II chasing Salamandra (with a small interruption of a party that Shani throws with Geralt's old friend Dandelion, which ends with Geralt possibly having sex with Shani). He investigates a murder, which leads him to believe that a mage is leading Salamandra. He opens an ancient tower (which the private eye instructed him to do), just to find some ancient texts. When he goes outside, he finds out that the private eye is actually Azar Javed, the mage, who knocks Geralt unconscious and takes the texts.
Geralt awakes in the personal chamber of Triss Merigold, in the rich quarter of Vizima. She has sex with him, wanting to 'examine his internal injuries. The rest of the chapter is spent uncovering the bases Salamandra has in Vizima, but also learning about a conflict between the Order of the Flaming Rose and the Squirrels, a gang of guerrilla freedom-fighting elves, dwarves, and other non-humans. He also begins uncovering another conspiracy concerning the royal seal. During a party of high-standing officials, Geralt meets Adda, who offers to have sex with him. Either if he accepts or declines, he not only finds letters in her chamber connecting her to Salamandra, but she either also hints it or his medallion shakes, which means that he is in the presence of an enemy.
Geralt finally attacks the base of Salamandra. He takes with him either Siegfried or a squirrel leader. He clears the base and then calls in either knights or elves, depending on who he brought with him, to fight Javed and the Professor. Javed separates Geralt and the allies, but Geralt presses on and duels the Professor. He wounds him, and just when he is about to kill the criminal a giant spider-like monster drops in and kills the Professor. Geralt causes a cave in, crushing the spider and its offspring, and then escapes. Outside, he finds himself surrounded by royal guards and Adda, who wants to shut him up.
However, Triss teleports him out of the situation and into a distant village. There, Geralt negotiates between the village and an aquatic city. At the end however, a battle begins between the Order and the Squirrels. The player can be neutral, help the knights, or the non-humans. When the battle is over Geralt, and Dandelion, who somehow appeared there with him, sail back to Vizima.
There, civil war has broken out. The Squirrels have caused a non-human uprising and the Order of the Flaming Rose wishes to end it. Depending on which side Geralt took in the previous battle, he can either be neutral and help the wounded get to hospitals with Shani, or help the knights or the elves in the battle. However, the Grand Master of the Order betrays the king, proving that he is the leader of Salamandra. He also curse Adda from a relapse of the striga curse, after which she marries a foreign king and forges an alliance between the kingdoms. The king tells Geralt to kill the Grand Master, and then Geralt can instruct the king what to do with the rebellion. Depending on which side Geralt took in the first battle, he can convince the king that the Order can still be loyal, convince him that the Squirrels are right, or convince him that they are both enemies. Then, again depending on which side Geralt took in the first battle, Geralt then either takes Siegried (Order), an elven leader (Squirrel), or Triss Merigol (neutral) on the hunt for the Grand Master. If he takes the Order path, on the journey to kill the Grand Master he fights and kills the elven leader. If he takes the Squirrel path, he does the same to Siegfried. With the neutral path, he meets both and he can either spare or kill them.
Fighting through some genetically altered knights of the Order (which the Grand Master made using the mutagens), going through the sewers and fighting a large monster, he and his partner near the Grand Master's home. There, Siegfried or the elven leader are wounded and Geralt goes alone, or he using a ruse to ditch Triss. Whichever the case, he goes in. Inside, the Grand Master explains to him his plan, of how the prophecies said that the world would eventually be consumed in ice and the only way for humanity to escape that is to go south, and how the Grand Master only stole the mutagens so he could make superhuman bodyguards to protect humanity on their journey. When Geralt does not believe him, the Grand Master casts an illusion and the witcher finds himself in a icy wasteland. He hunts the Grand Master, running into several ape-like monsters that are in fact what humans will evolve into when the ice comes, and summoning with his mind the allies that helped him throughout the adventure. At the end, he kills the Grand Master and escapes the illusion.
Back in the real world, in the ending cut scene, the king pays Geralt and the witcher walks away. But suddenly an assassin attacks the king. Geralt duels the assassin and kills him. When he pulls off the mask, he discovers that the man has vertical pupils, just like the witchers, setting the stage for The Witcher 2: Assassin of Kings