Hansel (Jeremy Renner) and Gretel (Gemma Arterton) have become Witch Hunters following their fateful encounter with one during their childhood, which caused scars in both of them. Gretel's are psychological - She is plagued by nightmares about the events. Hansel's are physical - He became diabetic from eating too much candy. He is also very cocky and enjoys having a good drink while bragging about his talents.
Their mother was killed by an angry mob that believed her to be a witch. Because of this, the two have lost a little of the passion and the thrill for the job, in addition to the fact that it gets easier and easier to kill witches. This changes when they are hired by the Mayor of the small town of Augsburg to rescue several children that have been captured by a coven led by Muriel (Famke Jensen), who wishes to sacrifice them in the next Blood Moon to gain immortality. The witches are aided by Trolls that do the handywork.
In addition to this, Hansel and Gretel also have to deal with the sadistic Sheriff Berringer (Peter Stormare), that has already killed several innocent women in his quest for the witches and plans to kill as many it is necessary to prove that he is better than them. Well-read, Sheriff Berringer easily manipulates the supersticious townspeople to believe that Hansel and Gretel have brought evil upon the land, causing them to become outlaws. The only ones who continue to aid them are the Mayor, a kind witch named Mina, who is saved from the burning stake by the duo and falls in love with Hansel; Benjamin Walsur, a 15-year-old fan of the two that wishes to become a Witch Hunter himself and, although still unexperienced, is very skilled; and their guide, Jackson.
With 48 hours to locate the witches' hideout in the extensive woods of Augsburg before the Blood Moon rises and both the sacrifices and Sheriff Berringer's bloodbath take place, Hansel and Gretel have to run against time to own to their reputation and destroy Muriel and her sisters.