A distant, remote scientific expedition taking place at the North Pole is invaded by a space alien who has reawakened after lying dormant for centuries after a crash landing. A cunning, intelligent alien who can shape-shift, thereby assuming the personality and form of anything and anyone it destroys. Soon, it is among the men of the expedition, killing each in turn and replacing them by assuming their shape, lulling the scientists one by one into inattention (and trust) and eventually, their destruction. The shape-shifting, transformed alien can pass every effort at detection, and the expedition seems doomed until the scientists discover the secret vulnerability of the alien and are able to destroy it.

According to science fiction historian Sam Moskowitz (1920-1997), Who Goes There? had a autobiographical impetus: Campbell's mother and aunt were identical twins and enjoyed teasing him in a game of substituting one for the other while in his care when they were infants and young children, thereby confusing him again and again with false (switched) identities. Moskowitz theorized that it was this game which lead to uncertainty of identity and clever masquerade which lead to feelings of helplessness and terror that Campbell funneled into what would be his greatest novel. This word is regarded as one of the greatest horror stories to emerge in the field of science fiction writing. It was also the basis for one of the great early science fiction films and its remake decades later.