In this article I situate Agamben’s theses on ‘inoperativity’ in dialogue with motifs drawn from Nietzsche’s discussion of the death of God and his conception of the ‘work of art without artist.’ I argue that Agamben helps us to get beyond the Existentialist interpretation of the human subject as creator of its own life (bios) by proposing an anarchic conception of giving artistic form to life (zoe) that deconstructs the position of mastery over life assigned to modern subjectivity and decentres the idea of the human agency in the process of creation. However, I also suggest that Agamben’s conception of the artistic life downplays or avoids other features of Nietzsche’s thinking on the death of God and creation that are tied to animality and the divinity of nature. In the first section, “The Work of Art without Artist and the Deactivation of the Artistic Machine” I discuss Agamben’s archaeology of the work of art and his thesis that since the Renaissance, the work of art has been produced through what he calls the ‘artistic machine.’ I examine his proposal to deactivate this machine by thematizing the dimension of human life he calls ‘inoperativity,’ and what this means for his understanding of the process of creation as anthropogenesis. I also raise the question of whether, by deactivating the artistic machine, Agamben may paradoxically be re-activating what he has previously called the ‘anthropological machine.’ The second section, “The Death of God and the Death of Man,” compares and contrasts the difference between Nietzsche’s and Agamben’s accounts of anthropogenesis and the relation between animality and divinity. It argues that the death God as the death of the human being in Nietzsche leads to a naturalistic conception of creativity inspired by Greek and Renaissance art that provides some insights into how to deactivate the ‘work-artist-operation machine’ without falling into the ‘anthropological machine.’ This article concludes with a third section, “Contingency, Resistance and Self-Overcoming” on the difference between Nietzsche’s and Agamben’s conceptions of contingency and resistance in the generation of a form-of-life. For Nietzsche a form of life is generated essentially in and through a process of continuous self-overcoming. In Agamben, a form of life is constituted through a dialectical tension between creation and resistance, the artist’s potential (impersonal) and potential not-to (personal). Whereas in Agamben the contingency of creation is located within the action, in Nietzsche creation happens to the activity as an event external to it.