Samuel Hayden was born to the powerful Hayden family and was a very prodigious intellectual and philanthropist. After he was appointed as General Director of the Global Science Council, the UAC recruited him. Soon after Argent energy was discovered on Mars, Hayden subsequently took over the leadership of the UAC.
After the Argent Tower was constructed in 2127, Hayden was diagnosed with an incurable brain cancer and left with a few months to live. Hayden avoided his death by transferring parts of his brain into a 3-meter tall mechanical body. It was implied that Hayden chose this form for his expeditions into Hell.
Hayden led the first manned expedition into Hell in 2145 in which he discovered the Doom Slayer, simply called "Doom Marine". He had the Marine recovered and kept him personally under his watch away from the auspices of his disgruntled colleague Olivia Pierce. Hayden's relationship with Pierce gradually deteriorated due to her deranged, religious obsession with Hell which ultimately corrupted her.
After Pierce betrayed Hayden and planned to open the gates of Hell, Hayden awakened the Doom Marine and tried to persuade him to assist him in stopping Pierce. However, he is harshly rebuffed twice at the beginning of the game, though Hayden claims to be willing to accept full responsibility for Hell's invasion. Hayden was able to gain the Marine's cooperation after cutting off his access to the satellite communications array and offering information that he seeks.
Hayden eventually meets the Doom Marine face-to-face in his office following the latter's return from Hell and the destruction of the Argent Tower. He explained to the Marine about the ongoing demonic invasion of the facility through the still-open Hell portal, and the need to pursue a new way into Hell in order to locate the Crucible, an artifact that can control the source of Argent energy known as "The Well," and stop Pierce's plans. He instructed the Marine to go to the Lazarus Labs to find the Helix Stone and a powerful weapon.
After the Doom Marine killed Pierce and stopped Hell's invasion, Hayden summoned the Marine to the facility via a dimensional tether. He then betrays the Doom Marine, taking the Crucible from him to continue exploiting Hell's resources for the sake of humanity's progress. Hayden admitted that he cannot kill the Doom Marine, but he will not allow him to stand in his plans, before teleporting the Doom Marine to an unspecified location. Before he does so, however, Hayden states his certainty that he and the Doom Marine would meet again.
- Despite having been diagnosed with "incurable brain cancer", Samuel Hayden had his frontal and temporal lobes transferred to his new body. It is possible that these parts of his brain were free of cancer, and that he chose to replace his whole body rather than simply replace the cancerous parts of his brain with cybernetic equivalents.
- Hayden's original human form can be seen in a hallway showing various scientists.
- He is literally immune to aging since his body is constantly maintained by stem cell and neuro-maintaining agents. However, he is not invincible. Currently, he is over 130 years old.
- S. Hayden has a phonetic similarity to "Satan", which may be foreshadowing that Samuel Hayden might be allied with the forces of Hell somehow (similar to Dr. Betruger of Doom 3.)
- When Hayden walks away to his office, the player is given control of his weapons, and can shoot Hayden. However, the bullets strike an invisible force field of sorts, dealing no damage to Hayden, who simply shrugs it off while telling the player to save their ammunition.
- His name is taken from a character cut from the Doom 3, but also appeared in the Doom 3 novels: General Hayden. Their personalities and history are not similar however, and only the name is recycled. It would also seem unlikely that they are related.
- Samuel Hayden along with the Doom Slayer is the only human being to have survived a trip to Hell and back.