Carolina and Juan Ángel “Johnny” Garza are twins living in a small Texas town on the US-Mexican border. Shortly after their 12th birthday, their mother disappears. Their father—Dr. Oscar Garza, a professor of history—is convinced she left him; the twins suspect foul play of some sort. This suspicion is made more sinister by the strange dreams and behavior that both Carol and Johnny begin to experience. When school breaks for summer, their father packs them off for Monterrey, Mexico, to stay with their mother’s family while he seeks professional help for his deepening depression. At the family’s ancestral home, the twins’ grandmother gives them their mother’s journal, and they learn the truth about themselves: they are naguales, shapeshifters. They are in the early stages of nagualism, shifting unintentionally during their sleep. They take turns keeping watch at night and discover that Johnny becomes a jaguar and Carol, a Mexican wolf.
Drawn by various clues, the twins visit the García Caves in the nearby mountain El Fraile, in Cumbres de Monterrey National Park. There they are approached by the tzapame, the Little People. One of them, a former human called Pingo, tells them the truth about their mother: she has been abducted by dark forces and taken into Mictlán, the Underworld. To save her, the twins must attempt to descend through the nine layers of the Underworld along a path called the Black Road, a dangerous trek that could cost them their lives. The tzapame give them several strange leather amulets with feathers, animal teeth, bones, etc. Additionally, the Little People hand them a clay jar with water and place a piece of jade in their mouths. Finally, they give them some jewels to offer the rulers of the underworld when they reach the end of their journey. The leader of the little people cautions, however, that the most important gift already lies within them.
Crossing through a smoking mirror of obsidian, Carol and Johnny find themselves in this dangerous land of the dead, their passage blocked by a great river; an enormous dog named Xolotl appears and helps them cross the river on its back. He asks about Pingo. From him Carol and Johnny learn that shapeshifter twins are very rare and that such children are often gifted with xoxal, a special sort of magic that—among other things—allows them to transform into any type of animal (rather than just one like most naguales). On the other side, they face a horrible climb up obsidian mountains. Xolotl keeps telling them to transform, but they insist they have no control. Frustrated, he turns into a human man and then leaves. They continue. At the top, they have to pass between two walls of rock that smash against one another in an attempt to crush them. Once through this, they find a terrible serpent blocking their path down. Faced with possible death, the twins unlock the secret to transforming at will. They defeat the serpent, but then the fierce alligator Xochitonal comes to avenge him. Xolotl appears again to hold it down and let them pass.
The twins then must traverse the nine deserts or layers of Mictlán. The first desert is utter darkness. Xolotl isn’t with them, as he’s still holding down Xochitonal. They remain shapeshifted to avoid pitfalls with their night vision. This level is utterly silent except for their own footfalls, and neither can speak since they’re in animal form. In the midst of the solitude, Carol is attacked by shadow magic, but manages to fend it off with a song her father used to sing to her. The twins discover that they can use xoxal to communicate mind-to-mind. The second desert is replete with jaguars and bats. Johnny transforms to draw them away, but is caught up in the pack mentality until Carol comes and breaks him free, having transformed into an enormous bat. She explains the use of the talismans to shapeshift into particular types of creature: all the twins have to do is grip a bit of animal matter (teeth, bone, feather) in their hand, and they can shift into that creature.
In the third desert, tornado-like snowstorms chase the twins until Xolotl appears and rescues them. He helps them understand their abilities better, but then leaves, telling them they must overcome the remaining obstacles on their own. In the fourth desert, amidst massive ruins of buildings that pre-date humanity, the twins must face what appear to be phantoms of their loved ones, each recriminating them for their shortcomings. Through Carol’s newfound song sorcery, the twins discover that these are just forms assumed by the fierce Ixpuztec, a pterodactyl-like demon. Johnny shifts into a screech owl and Carol into a snatch bat, and they just barely managed to fly away in time.
When they reach the fifth desert they find lava plains and dragon-like creatures. Carol is captured by one and taken to Huitzilopochtli, the chief Aztec god. He tries to tempt her into helping him wage war against Tezcatlipoca, but then Johnny appears, transformed into a charm of hummingbirds, and knocks the god into a river of magma. They fly over the lava plains, narrowly escaping plumes of flaming gas and hungry demons. Waiting for them in the sixth desert is the evil Nextepehua, the smoking demon who scatters clouds of ashes. Using the clay pot of water, the twins reduce the demon to a screaming pile of slurry.
In the seventh desert, the twins reach the capital city of Mictlan: Xibalba. There they are sacrificed by the Ajalob, ruling demons, their hearts supposedly removed; they’re helped by the goddess Ixcuinan and the four Ahuiateteo, and escape the city before the demons eat the jade pieces the Little People gave the twins. The eighth desert is bleak, with howling winds full of obsidian knives. They shapeshift into thick-skinned creatures (a crocodile and an armadillo) and get through it. As they are finally passing over a narrow path of stone that bridges the black lake of Apanhuiayo, whose rotten stench nearly makes them faint, attacking demons make Johnny fall in and harry Carol. The twins use the last strange bits on their amulets: he shifts into the ahuizotl or water dog; she becomes a harpy and rends the attackers to bits.
Finally they stand before the Lord and Lady of the Underworld and present them with gifts (the jewels provided by the Little People) in order to gain admittance to the heart of their realm. There they find their mother, a captive of the evil Tezcatlipoca, a dark god who wants to bring about the destruction of the world. Carol and Johnny discover their xoxal magic is one of the tools that could assist or ruin Tezcatlipoca’s plans. The dark god kidnapped their mother in order to try to destroy the twins, spiritually or physically. Their love for their mother, however, keeps them from despair and triggers their latent magic. They dispel Tezcatlipoca, and the three are guided back to the land of the living by Xolotl, emerging at the Cola de Caballo falls. They are finally reunited with their father, and they reveal their true nature to him.