Bo was born in the early 1970s to famous wax sculptors. As a child, Bo misbehaved far worse than most kids and would often try to attack his parents. Later on, Bo was the owner of a gas station in the town of Ambrose before it became deserted. Later on, he and his brother began to lure people into the deserted town and would proceed to kill them and coat them in hot wax to make life-like wax sculptures.

In 1974, Trudy Sinclair, a famous wax sculptor is sculpting while her son Vincent is eating cereal. All of a sudden her husband, Victor Sinclair comes into the kitchen with their other son Bo, who is kicking and screaming in his father's arms. He is strapped into his high chair and once again misbehaves by kicking the table causing his mother's sculpture to fall on the floor and break as he scratches his mothers hand to which she replies by slapping him across his face.

Sometime before the events of House of Wax, there was a isolated town named Ambrose where Bo was the owner of the gas station. Ambrose had been abandoned when the local sugar mill shut down. However Bo and his brothers stayed in the town and begin to lure victims to the town and would turn them into wax sculptures for their wax museum.

In present day, six friends in 2005—Carly Jones, her twin brother, Nick, her boyfriend, Wade, her best friend, Paige, Paige's boyfriend, Blake, and Nick's friend, Dalton—are on their way to a football game in Louisiana. They decide to camp for the night and pull off to the nearby wooded area. As they are getting situated, a stranger in a pickup truck visits their campsite, shines his lights and refuses to leave or address them until Nick smashes one of his headlights. The next morning, Wade discovers that his car's fan belt is broken. Carly and Paige wander into the woods, where Carly tumbles down a hill and falls into a pit filled with rotting animal carcasses. After rescuing her, the group meets a strange, rural man named Lester, who offers to drive Carly and Wade to the nearby town of Ambrose to get a new fan belt, while the rest of them go to the football game.

Upon arriving in Ambrose they find the town virtually deserted and began to become suspicious about Lester when she notices the broken headlight on his truck. Unable to find an attendant at the gas station, they wander into the church, disrupting a funeral. There, they meet a mechanic named Bo Sinclair, who offers to sell them a fan belt after the funeral. While waiting for the services to end, Carly and Wade visit the 'House of Wax', a wax museum which itself is made of wax and is the central feature of the town. The gas station does not have the right size fan belt, so they follow Bo to his house. Carly waits outside as Wade heads in to use the bathroom however, he is knocked out by Bo's twin brother Vincent Sinclair who wears a wax mask to hide his disfigured face. Carly soon realizes her suspicions were right and flees the area to look for help as Bo sees this and runs after her. She returns to the church but finds everyone just to be wax figures. Bo finds her and locks her in the gas stations cellar and glues her mouth shut as Vincent back at the house coats Wade in hot wax turning him into a figure but not killing him. 

Meanwhile, Nick, Dalton, Paige and Blake realize they will not arrive at the game in time and return. Nick and Dalton arrive in Ambrose to find Carly and Wade. Nick finds Bo and asks of his sister's whereabouts as Carly tries to get his attention, Bo cuts off the tip of her pointer finger to shut her up, but she uses the blood to unglue her lips and alerts Nick just as Bo is about to attack him and Nick fends him off and saves Carly and the two escape with Bo still on the chase. Meanwhile Dalton finds the wax museum and wanders inside and finds Wade who is stuck in place and begins to peel off the waxing trying to hep but this causes him to indirectly pull his face off. Vincent appears and tries to hit Dalton but hits Wade and kills him and later decapitates Dalton. He also later kills Paige and Blake as Bo hunts down Carly and Nick.

Nick and Carly realize that all of the town's inhabitants are real people covered in wax; Bo and Vincent have been luring people in and covering them in wax to make the figures look more realistic. Nick and Carly return to the house to find Wade and Dalton. When Bo and Vincent return, they chase Carly and Nick to the House of Wax. It is revealed that Bo is the "evil" twin and Vincent is the "good" twin; following their parents' death, Bo has been controlling the more mild-mannered Vincent through physical and verbal abuse.

The chase begins in the House of Wax as Nick accidentally sets the house on fire which results in the place beginning to melt. Bo attacks Carly who bludgeons him to death with a baseball bat as a enraged Vincent tries to fight them off he is overpowered and falls through the floor landing on top of Bo's body as Carly and Nick barely escape as Vincent and Bo's bodies are buried under the molten wax ending their reign of terror.

The next day, the police arrive and report that Ambrose had been abandoned for ten years when the local sugar mill failed. As Nick and Carly are taken to a hospital, the Sheriff learns that Mr. and Mrs. Sinclair had a third son. From inside the ambulance, Carly sees Lester (who is supposedly the third brother) who smiles and waves goodbye as the ambulance van leaves the town. It is possible that Lester is actually in charge of luring victims into Ambrose. It is unknown what kinds of relationship Lester has with his twin brothers but based on the fact he shows no sadness in their death indicating that the relationship is poor.