In a remote jungle land long ago, Kuzco (voice of DAVID SPADE) is the young, arrogant and insensitive emperor who's focused only on himself. His latest selfish endeavor is to build a summer retreat on a hill currently occupied by Pacha (voice of JOHN GOODMAN) and his peasant family. His only real problem is with Yzma (voice of EARTHA KIT), his older high priestess who enjoys filling in for him in his absence, usually without his permission.
When Kuzco catches her doing this one too many times, he decides to fire her, but this only increases her quest for his throne. As such, she has her hulky and easily distracted, right-hand man, Kronk (voice of PATRICK WARBURTON), poison the emperor, who has no heirs, so that she can become the empress.
Unfortunately, Kronk uses the wrong potion and instead of Kuzco ending up dead, he turns into a talking llama. Shocked at this turn of events, Yzma orders Kronk to kill this aberration. While attempting to do just that, however, Kronk has a change of heart and Kuzco then inadvertently ends up on Pacha's cart with that peasant unknowingly taking the llama back to his home, where his wife, Chicha (voice of WENDIE MALICK) and their two young children await him.
It doesn't take long, however, for both Pacha and Kuzco to discover what's happened, and the emperor -- in llama form and unaware of the treachery in his ranks -- orders Pacha to return him to the palace. Pacha agrees to do so, but only if Kuzco agrees to build his summer home somewhere else so as not to displace his and others' families.
Still self-centered, Kuzco refuses, but soon realizes that he'll truly need Pacha's help to make it back to the palace. From that point on, Pacha tries to do just that, all while avoiding Yzma and Kronk who are determined to finish off the emperor before he has a chance to regain his throne.