Santanico (Eiza Gonzalez) confronts Malvado (Esai Morales) with Seth’s (D.J. Cotrona) help, while Richie (Zane Holtz) and Kate (Madison Davenport) must stop Carlos (Wilmer Valderrama) and Scott (Brandon Soo Hoo) from overturning the ancient prophecy and taking control of a powerful evil.
In 1912, a group of miners are seen digging under a well but when Prospector, one of the miners decides to go deeper into it, he releases a hidden pool of blood. He walks out possessed and kills the rest of the miners. In present day, Malvado brings out a captive Kate whom he uses to find out Carlos's whereabouts, and sends her and Richie after him to retrieve the ancient key. Paloma, who has been turned by Malvado, tells Santanico that he is departing to El Rey and a mysterious individual is making his way to Jacknife Jed's. Carlos finds the blood well and uses the ancient key to unlock the pool of blood. Richie and Kate arrive at the well, and after she tries to reach Scott, Carlos shoots her. Santanico and Malvado finally confront each other and he poisons her with his venom making her fall into an unconscious state. Malvado attempts to leave for El Rey with Santanico but she engages in a fight with and kills him with the help of Seth.
- Unnamed Culebras-shot; killed by Seth Gecko & Richie Gecko
- Paloma Gutierrez-staked; killed by Santanico Pandemonium
- The Arbiter-dismembered; killed by other culebras
- Amancio Malvado-snake was slit; killed by Santanico Pandemonium
- This episode marks Demi Lovato's appearance as Maia.
- Richie and Kate work together in this episode.
- Paloma was turned into a culebra by Amancio and she was convinced she could take Santanico's place as queen and as a diosa (goddess).
- Kate and Richie share a blood bond and he sees into her soul.
- Amancio is killed by Santanico, who proceeds to disembowel him and rip his snake out, then kill his snake by slitting it with her weapon.
- Richie references the 1973 film, The Exorcist, when he thought Kate was going to spew pea soup at him.
- In his culebra form, Amancio is seen to look more snake-like and has outer blades in his arms for defense.
- Kate was shot twice by Carlos after trying to get to the blood, but is seen still alive in Santa Sangre's promo.
- There are two separate flashbacks, one in 1912 and the other in 2008.
- The Prospector appeared in this episode after a mention in Bizarre Tales by Celestino.
- Sonja, The Regulator, Freddie and Celestino are seen in archive footage.