Over the course of the 19th century, the existence, status, and individuality of the human soul came under considerable reassessment at the interstices of theology and science. Religious views inherited from the past, including the notion of an immaterial mind in concert with, or in alienation from, a material body, became harder to defend as the study of brain function advanced within science. The birth of the field of psychology, literally, “the study of the soul” came into its own as a discrete discipline precisely as a positivistic and materialistic assessment of the human was reaching its ascendancy in transatlantic thought. A gradual series of shifts took place, wherein the soul was equated with the mind, which in turn was increasingly reduced to the physical brain and its functions. This paper explores phrenology as one of the key phenomena influencing constructions of human nature over this period. The rise of phrenology, which sought to make conclusions about human personalities via the examination of bumps on the skull and the shape of the underlying brain, held court for much of the middle part of the century. Here I shall argue that phrenology is a case where secularized accounts of the embodied person portrayed not a simple and unidirectional shift into materialism, but rather a distorting of theology through the assumptions of an increasingly popularized version of phrenology. While early founders of phrenology such as Gall and Spurzheim sought to ground its scientific claims in a materialistic account of the human brain, later popularizers of phrenology, such as Combe and Fowler, found themselves needing to broaden its appeal. This broadening dynamic required interaction with religious categories, with theological assumptions at play in American culture, and with religious promoters of a wide range of social reforms with which phrenology became increasingly allied.