From Dusk Till Dawn starts after the brothers, Seth and Richard “Richie” Gecko, retrieve a map from a liquor store after they have robbed a bank. They encounter the Texas Ranger Earl McGraw who tries to prevent them from escaping. The brothers exchange shots with him and manage to kill the ranger in the process. The brothers get away but not without Richie suffering from a gunshot wound in the hand. They proceed with their plans and make their way to Mexico to start a new life.
In the motel where the brothers are staying, a pastor named Jacob Fuller checks in with his daughter and her adopted son. The brothers take Jacobs’s family as hostage and force him to drive them to the Mexican border. They manage to pass the border’s security and they head toward a club where the brothers are to meet their contact.
Inside the club, the group stay to watch a performance by an entertainer named Santanico Pandemomium. An altercation with some people leads to a stabbing on Richie’s already wounded hand. When the blood starts pouring out, Santanico changes into a vampire and starts sucking all the blood from Richie.
It turns out that the rest of the employees of the bar are all vampires. Seth and his group, fight off the vampires along with other customers, Frost and Sex Machine, inside the bar. Armed with wooden stakes and crosses, the remaining humans try to concoct a plan on how they can beat the vampires.
Later on, they discovered that Sex Machine has already been turned. Sex Machine kills Frost and Jacob before Seth and the rest of the group get rid of him. With some of his friends gone, Seth and Jacob’s family prepare themselves for another battle with the vampires. They have no choice but to kill those that are bitten and turned into vampires, including Jacob.
As the suns begins to rise, only Seth and Jacob’s daughter, Kate, are left. Using up their remaining bullets, they shoot holes on the walls of the bar to let the sunlight in. The vampires start burning and they completely perish when Seth’s contact, Carlos, arrives with some people and blows the door from the outside letting more sunlight penetrate the place. Seth haggles with Carlos regarding his fee though the latter has not an inkling of idea about what has happened. Though Kate wants to stay with Seth during his journey, the two part ways.
The movie ends revealing that the spot where the bar has stood is part of an ancient Aztec temple filled with things of the people who has fallen victim in the place.