The overriding atmosphere pervading this work is one of squalor and depravity. The depraved actions of the protagonist, Franz Biberkopf, and his chief antagonist, Reinhold, are echoed by the depravity of the Alexanderplatz region of Berlin itself. Through the frequency and indelicacy with which sex is represented, together with the vivid descriptions of violence (as for instance during a scene portraying the workings of a slaughterhouse), the author weaves a picture of Berlin that seems, in the words of critic Jeff Tompkins, "A deliberate affront to contemporary sensibilities." Even the language of the work has a crude and aggressive quality stemming from a prevalence of obscenity and slang; this has historically rendered the work difficult to translate.

Above all else, the narrative evokes the crowded and chaotic nature of Berlin in the Jazz Age. Something of the rhythm and melodies of jazz music is conveyed through the frequent inclusion of newspaper clippings, weather reports, and political slogans—not to mention the novel's various diversions on topics as varied as astronomy, theology, and cooking. Alred Döblin's inclusion of the work's principal setting as part of its title necessitates that the setting adopt a central role, and these frequent diversions serve to establish what writer Dustin Illingworth terms the "urban chorus" of Berlin in the latter years of the Weimar Republic.

Running parallel with this work's other primary motifs is the theme of moral redemption, whereby Franz undergoes a succession of punitive experiences—comparable to the biblical plagues of Egypt in their escalating severity—before finally realizing the error of his ways. At the opening of the novel, his reluctance to leave the security and stability of prison life indicates immaturity and an unreadiness to face the temptations of life, which is soon realized by his slump back into a life of crime and immorality. The work's concluding statement—"We know what we know, we had to pay enough for it"—highlights how far Franz subsequently has to come in order to reach moral and spiritual maturity. Miez constitutes a sacrificial lamb who innocently suffers the fate that Franz has earned and whose death will prove instrumental in awakening Franz to one of the key lessons he will have learned by the end of the novel: how to feel responsible for his own actions. The most severe punishment Franz undergoes, the loss of an arm, is itself symbolic, recalling the advice offered by Jesus Christ in Mathew 5:30:

And if your right hand causes you to sin, cut it off and throw it away.

The arm Franz loses is the same arm with which he has practiced his various misdeeds. Without it, he is purified and ready to start the virtuous life he initially desires on leaving prison.