The main character and silent protagonist of the game. Isaac Clarke is a ship system specialist and an engineer traveling aboard a small repair shuttle, the USG Kellion, to investigate the USG Ishimura. He is accompanied by the shuttle's commander, Captain Zach Hammond, the shuttle's pilot Corporal Chen, the shuttle's co-pilot Corporal Johnston, and a computer specialist, Kendra Daniels. Unfortunately for them, they are thrust into the middle of the nightmare that the USG Ishimura has become. The crew has been converted into creatures known as Necromorphs and now Isaac, while separated from his team from the very start of the game, must fight the alien creatures off on his own all while running around the ship to repair damaged systems. Isaac Clarke continues to search for his girlfriend, who is his reason for requesting to join the USG Kellion on the repair mission. Her fate for the majority of the game is unknown. Throughout the game, Isaac stumbles across a conspiracy involving the Church of Unitology, the Government and the mysterious divine relic the Marker.
From logs unlocked after the completion of the game, It is implied that Clarke's mother, Octavia Clarke is a high ranking member of The Church of Unitology (Vested level title). Isaac is the only non-speaking character in Dead Space; he only grunts and screams.