Harry is a 32 year old writer. His wife, who still remains unnamed, died four years before the first game. Three years before she died, they found a child on the side of the road outside of Silent Hill, took the child home and named her Cheryl. For the next 7 years, Harry takes care of Cheryl up until the events of the first game. Harry and Cheryl then decide to take a vacation to Silent Hill. While Harry is driving towards the town late at night with Cheryl in the front seat, he sees a young woman walk into the path of his vehicle. He tries to avoid her but loses control of his Jeep and crashes into a ditch. A few hours later in the morning, he awakens to find Cheryl missing. This is where the game starts off. Harry Mason is the archetypal Silent Hill protagonist. As such he deviates substantially from other classic video game protagonists. He is clumsy, and it is obvious he has never received training in survival or the use of firearms, a deficit which serves both the realism of the game and the horror it attempts to induce in the player. Harry is the father of Heather (the main character of Silent Hill 3). He was brutally murdered in Silent Hill 3 by the Missionary under Claudia Wolf's order.

Cybil is a police officer from Brahms, a town neighboring Silent Hill. She was sent to investigate her precinct's lack of communication with the Silent Hill police and was unwittingly drawn into its strange world. Unlike the other human characters, Cybil is a Skeptic and has difficulty accepting the paranormal activity in town. She quickly befriends Harry Mason and helps him to find his daughter. Judging by Cybil's remarks, she is also unaware of the Otherworld that Harry has been to, suggesting that she is an 'outside player' in all of this.Much later in the game, Cybil shows up again in the antique shop right after Harry has been to the "Otherworld" of Silent Hill. Here she explains that the police were investigating the flow of drugs in Silent Hill, which she attributes to all the weird things going on.

Dr. Michael Kaufmann is the director of medical staff at Alchemilla Hospital. While he merely refers to himself as someone who "works" at the hospital, Kaufmann is a close associate of the Cult in Silent Hill (The Order). Kaufmann arranged Alessa's birth and medical care after her immolation at the age of seven. As reward for assisting the cult, Kaufmann deals in the hallucinogen PTV, derived from a local plant called "White Claudia".  He dispenses this drug to tourists as well as Lisa Garland, one of his nurses. Lisa is forced to care for Alessa in the hospital basement against her will, under the threat of drug withdrawal. After Dahlia Gillespie immolated her daughter in a dark ritual, she took Alessa to the hospital to be kept there out of sight until she could give birth to the cult's "God". Kaufmann is displeased with having to keep the girl stabilized and housed in the basement for an indefinite period. Perhaps in mistrust, he keeps samples of aglaophotis, a substance capable of exorcising demons, in his office and in the gas tank of a motorcycle to be hidden from the cult.

Dahlia Gillespie is the leader of The Order, a doomsday Cult that worships angels, particularly fallen ones. Although her given age is 46, her physical appearance looks much older than that. Dahlia is the mother of Alessa, whose presence has summoned Poltergeist activity since she was a child. These disturbances, along with Alessa's latent telekinetic powers, saw her branded her a witch by her classmates. Dahlia knew her daughter's powers were linked to the dark "God" which Silent Hill's cult worshipped. Hoping to "birth" her god through Alessa, Dahlia used occult rituals to impregnate her daughter. To expediate the summoning of God, Dahlia set their house on fire with Alessa trapped inside. Although the fire was ruled an accident, Alessa was left completely disfigured from the resultant burns. Through the use of a magical incarnation invoked by her mother, Alessa lingered despite her injuries (which should have been fatal) and was placed in the care of Dr. Micael Kaufmann, a cult affiliate. While the constant torture of her wounds helped refine Alessa's reality-bending powers, she resisted being used as a container for the 'God', and her soul split in two halves, using a form of Bilocation in order to escape her torture. Her other form, a newborn was discovered by Harry Mason and his wife, who named her Cheryl and raised her as their own.