William Dyer is a geology professor at Miskatonic University who leads an extensive, well-equipped scientific expedition to Antarctica in 1930. Priding himself on rational thought and scientific rigor, he originally travels south expecting to simply collect geological specimens. His understanding of the world is severely challenged by the group's discoveries, prompting him to recount his experiences as a warning to others.

Professor Lake is a biologist and a leading figure in the Antarctic expedition. Driven by professional ambition, he acts on a strong hunch and diverges from the main group to investigate unusual fossils in a distant region. His eagerness to make a groundbreaking biological discovery drives him to take significant risks in the ice.

The Old Ones are an ancient, highly advanced alien race that colonized Earth tens of millions of years ago. Exhibiting traits of both plants and animals, they have star-shaped heads, wings, and a biological makeup that defies human scientific classification. They are responsible for the vast, monolithic architecture hidden behind the towering Antarctic mountains.

The Shoggoths are artificial, formless entities composed of viscous black slime. Originally engineered by the Old Ones to serve as a biological slave workforce, they can mold their bodies into any necessary shape or organ required to construct monumental cities. They possess immense physical power and a disturbing lack of a fixed physical form.

Danforth is a young graduate student who accompanies the Miskatonic University expedition. As a junior member of the party, he shows deference to the older professors and demonstrates a keen eagerness to learn. His academic curiosity makes him an active participant in the team's aerial surveys of the towering, black mountain range.

Professor Pabodie is a scientist from Miskatonic University who participates in the Antarctic trip. He contributes to the team's early success by inventing a specialized, lightweight drill that helps the crew collect deep geological samples from the ice.

Atwood is a physicist attached to the Miskatonic University expedition. He works alongside the other department heads to establish the initial string of camps and survey the uncharted Antarctic environment.

Gedney is a member of Professor Lake's splinter group that explores the northwest mountain range. When the main expedition team arrives at Lake's location, they find Gedney absent from the destroyed site, prompting a search of the surrounding icy terrain.