"Prequel" to the first From Dusk Till Dawn is set in Mexico in the early 1900's which begins with the escape of Johnny Madrid, a dangerous local outlaw, from the gallows who then kidnaps his hangman's beautiful daughter, Esmeralda, with a little help from Reece, a female outlaw from the U.S. With the hangman and a local posse on their trail, Johnny meets with his gang who all rob a stagecoach which contains American author Ambrose Bierce along with newlywed couple John and Mary Newlie. As night falls, all parties coincidently seek shelter in an isolated inn/whorehouse which is run by vampires led by the high priestess Quixtla who targets Esmeralda. Esmeralda is revealed to be the half-human, half-vampire princess Santanico Pandemonium, whom the vampires want as their heir in which all the humans must join forces if they are to survive the night from the vicious blood-suckers.

The highly skilled Federale Machete is hired by some unsavory types to assassinate a senator. But just as he's about to take the shot, he notices someone aiming at him and realizes he's been set up. He barely survives the sniper's bullet, and is soon out for revenge on his former employers, with the reluctant assistance of his brother Cheech Marin, who has become a priest and taken a vow of nonviolence. If you hire him to take out the bad guys, make sure the bad guys aren't you!

Lester and Carolyn Burnham are on the outside, a perfect husband and wife, in a perfect house, in a perfect neighborhood. But inside, Lester is slipping deeper and deeper into a hopeless depression. He finally snaps when he becomes infatuated with one of his daughter's friends. Meanwhile, his daughter Jane is developing a happy friendship with a shy boy-next-door named Ricky, who lives with a homophobic father.