Kagome is the grand daughter of the keeper of Higurashi Shrine, a shintō shrine near Tokyo. On her fifteenth birthday, she is pulled into a well (The Bone Eater's Well) by a centipede yōkai (demon), known as the Mudake Jōrō (Mistress Centipede), and is taken into feudal Japan, specifically the Sengoku period. In the past, she finds a sleeping half demon who is pinned to a tree by an arrow. She is captured and taken into the nearby village and is confronted by Kaede, the shrine maiden of the village. Kaede at first thinks that Kagome is a demon, due to her strange-looking modern clothing, but she changes her mind when she notices that Kagome bears an uncanny resemblance to her long dead sister, Kikyō.

That night, the centipede demon attacks the village, and Kagome flees into the forest where Inuyasha is pinned. This time, however, he is awake and calls her "Kikyo". When the centipede demon catches up to Kagome, the villagers unsuccessfully try to defeat it. When the centipede bites Kagome, the Shikon no Tama (The Jewel of the Four Souls) falls from her wound and is eaten by the centipede. Kaede realizes that Kagome is Kikyo's reincarnation, as the Shikon no Tama was burned with Kikyō's body 50 years ago. Inuyasha, the hanyō, then asks Kagome to remove the arrow so that he can slay the demon and recover the Jewel for himself. She does so, and Inuyasha defeats the demon, but then demands that she hand over the Jewel to him, for the Shikon no Tama has the power to grant anything that the user desires.

As Inuyasha advances on Kagome, Kaede magically summons kotodama no nenju (rosary beads; lit. "power of the spoken word" or "prayer beads", as some people call them) around his neck that binds him so that whenever Kagome says a certain command, Inuyasha is instantly forced to the ground. In the Japanese version the word is 'osuwari' (お座り, sit), and in the English versions "sit" or "sit, boy" are used. This is an intentional joke as Inuyasha is an inugami, and 'osuwari' in Japanese is a command that is generally given to domesticated dogs to make them sit. However, it should be noted that, in some cases, she has used the command in order to save his life (such as making him hit the ground to avoid an incoming attack. It's usually used to stop Inuyasha from charging or if he is unaware, though both will cause Inuyasha a certain amount of grief). She uses "Sit, boy!" more often in the anime, though.

The day after their chance meeting, a demon-crow attacks and swallows the Jewel, forcing Kagome and Inuyasha to attempt to retrieve it together. During the battle, Kagome shoots an arrow at the crow, using a piece of its flesh (it's foot) to assure accuracy, as the body parts are attracted to each other when severed. The arrow strikes and shatters the Shikon no Tama into many shards ("Shikon no Kakera") that are scattered across Japan and even to worlds beyond.

Kagome then sets out with Inuyasha to recover the shards so that other demons cannot use it for malice (though Inuyasha consistently claims his true intention has always been to become a full demon using the Jewel), occasionally returning to the modern era for supplies or because she and Inuyasha get angry at each other. On their journey they meet many people and pick up many friends and companions along the way.

The focus of the journeys of Kagome and her companions changes slightly as they learn about the presence of Naraku, an evil half demon that has not only greatly disrupted the lives of each of Kagome's friends but also seeks the Shikon Jewel for himself.