London's story is a tale of survival and a return to primitivism. Pizer writes that: "the strong, the shrewd, and the cunning shall prevail when ... life is bestial".
Pizer also finds evident in the story a Christian theme of love and redemption, as shown by Buck's refusal to revert to violence until after the death of Thornton, who had won Buck's love and loyalty. London, who went so far as to fight for custody of one of his own dogs, understood that loyalty between dogs (particularly working dogs) and their masters is built on trust and love.
Writing in the "Introduction" to the Modern Library edition of The Call of the Wild, E. L. Doctorow says the theme is based on Darwin's concept of survival of the fittest. London places Buck in conflict with humans, in conflict with the other dogs, and in conflict with his environment—all of which he must challenge, survive, and conquer. Buck, a domesticated dog, must call on his atavistic hereditary traits to survive; he must learn to be wild to become wild, according to Tina Gianquitto. He learns that in a world where the "club and the fang" are law, where the law of the pack rules and a good-natured dog such as Curly can be torn to pieces by pack members, that survival by whatever means is paramount.
London also explores the question of "nature vs. nurture", according to Pizer. Buck, raised as a pet, is by heredity a wolf. The change of environment releases his innate characteristics and strengths to the point where he fights for survival and becomes leader of the pack. Furthermore, Pizer maintains that the story appeals to human nature with the theme of the strong prevailing, particularly when faced with harsh circumstances, and a return to the wild.
The veneer of civilization is thin and fragile, writes Doctorow, and in the story London exposes the brutality at the core of humanity and the ease with which humans revert to a state of primitivism. His interest in Marxism is evident in the sub-theme that humanity is motivated by materialism; and his interest in Nietzschean philosophy is shown by Buck's characterization. Gianquitto writes that in Buck's characterization, London created a type of Nietschean Übermensch – in this case a dog that reaches mythic proportions.
Doctorow sees the story as a caricature of a bildungsroman – in which a character learns and grows – in that Buck becomes progressively less civilized. Gianquitto explains that Buck has evolved to the point that he is ready to join a wolf pack, which has a social structure uniquely adapted to and successful in the harsh arctic environment, unlike humans, who are weak in the harsh environment.