The Loomis family is one of the main families in the Scream series. They feature as the main antagonists of the first two films, and were mentioned frequently in the third and fourth.
- Hank Loomis: was the father of Billy Loomis and the husband of Debbie Loomis. Hank is best known for his secret affair with Maureen Prescott, causing Debbie to leave Hank and Billy. It is because of this that Billy, blaming Maureen, killed Maureen and set off a chain reaction of events. Hank did not care much for his son or his ex-wife. After both of them died, Hank is not shown in the series again in person. It is due to his sleazy actions that the events of the films took place.
- Debbie Loomis: was the mother of Billy Loomis and wife of Hank Loomis. When her husband had an affair with Maureen Prescott, Debbie moved out, leaving Hank to raise their son Billy on his own. After Sidney defeated and killed Billy as a result of Billy's vengeful murder spree, Debbie swore revenge and recruited Mickey Altieri to help her kill Sidney and Gale Weathers for her involvement by orchestrating a copycat Ghostface murder spree. They killed many people close to Sidney, including Randy Meeks because he badmouthed Billy, but were unable to kill Sidney ultimately. Debbie betrayed and shot Mickey to frame him as the sole killer, but right before she could exact her revenge on Sidney, Cotton Weary held her at gunpoint. Debbie attempted Cotton to help her and to let her kill Sidney and he'll get what he wanted, when he refused to help her, she reminded him that Sidney sent him to death row in prison for a year. Still refusing, Cotton shot Debbie in the chest. After Sidney and Gale kill Mickey, Sidney shoots Mrs. Loomis in the head because "just in case".
- Billy Loomis: was the son of Hank and Debbie. Billy met Roman Bridger, a young music video director, one fateful day and Roman showed Billy a tape of an affair between his father, Hank, and the mother of Billy's girlfriend, Sidney. Roman manipulated an enraged Billy into killing the mother, Maureen Prescott, alongside his best friend, Stu Macher. They framed Maureen's lover Cotton Weary for the murder. A year later, Billy and Stu masterminded a killing spree in Woodsboro, the ultimate target being Sidney, for unknown reasons. They planned to kill Sidney and frame her father, Neil Prescott. Using a Halloween costume, a voice changer, and a knife, they executed a killing spree as planned, up until the "grand finale" at Stu's house. Billy was about to finish his genius plan by killing Sidney when local reporter, Gale Weathers, shot him. Billy survived the gunshot but feigned death, and made a second attempt moments later. However, just as Billy opened his eyes and grunted, Sidney shot her psychotic boyfriend in the forehead, killing him for good.