The prequel is set in Mexico in the early 1900s and begins with an American author, Ambrose Bierce, experiencing a nightmare in which he dies at the hands of Pancho Villa. Bierce wakes and talks to a local bartender about his intentions to join Pancho Villa's revolutionary army. He joins a stagecoach transporting a newly-wed couple, John and Mary Newlie, who are traveling to Mexico to preach Christianity. Meanwhile, Johnny Madrid, a dangerous local outlaw, escapes from the gallows and kidnaps his hangman's beautiful daughter, Esmeralda. Madrid receives assistance from Reece, a young woman who wants to become Madrid's apprentice as an outlaw. With the hangman and a local posse on their trail, Madrid meets with his gang. They later rob Bierce's stagecoach because of Reece's belief that Bierce possesses an invaluable object. The object turns out to be the manuscript for Bierce's new book. Annoyed by this, Madrid leaves Reece to die in the desert. She is found by the posse who use her to track the two.
As night falls, all the parties coincidentally seek shelter in an isolated inn that also serves as a whorehouse. They meet Ezra Traylor, a businessman heading to the U.S. The hangman is the only one who knows that the establishment is run by a group of vampires led by the high priestess, Quixtla, who targets Esmeralda. As night falls John gets into a fight with one of Madrid's men, drawing blood. The vampires eventually reveal themselves, lock the exit and attack the patrons. All of the hangman's men and the remnants of Madrid's gang are killed by the vampires. Ezra is overcome by vampire women, is fed on and quickly turns. His newly-undead form grabs the helpless Mary and bites her. Madrid, Bierce, Reece, John, Esmeralda, the hangman and one other patron manage to escape into the dungeons beneath the building and try to work together to find a way out.
Mary rises as a vampire and goes after the group, revealing that John is a fraud who has only married Mary for her father's money. John is eventually forced to kill her. The patron who escaped with them hides a bite he had received from a hooker earlier. As they continue through the catacombs, he turns and bites John. John kills the patron. Doomed, he persuades Madrid to stake him to prevent him turning. As the remaining survivors keep going, Reece confesses to Bierce that she is an outlaw who has killed her entire family. The group eventually ends up back at the bar entrance, only to find Quixtla and the vampires in wait for them. She reveals that Esmeralda is a half-human, half-vampire princess, Santanico Pandemonium (Salma Hayek's character in the original From Dusk till Dawn), and the daughter of Quixtla and the hangman. The hangman had taken her away in the hope of raising her as a normal human but, thanks to his mistreatment and Madrid's kidnapping, she has been led back to Quixtla.
Madrid, the hangman, Bierce and Reece are hung upside-down to be fed on later as Quixtla transforms Esmeralda into the vampire princess. Madrid manages to break from his bonds and free the others. Reece is bitten in the scuffle and presumably becomes a vampire. Esmeralda bites and turns the hangman into a vampire, but he manages to open the entrance way and kill Quixtla before the change is complete, allowing Madrid and Bierce to escape. As the film ends, Esmeralda screams for Madrid not to leave her as the entrance is closed. Madrid looks away sadly and joins Ambrose's quest to join Pancho Villa's army. As they leave, the camera zooms out to show the Mayan temple behind the building that houses the vampires, a reference to the first film.
Who kills Bierce in his nightmare?
Pancho Villa