ABSTRACT: Daily practices put humans in close contact with the surrounding environment, and differences in these practices have an impact on human physiology, development, and health. There is mounting evidence that the microbiome represents an interface that mediates interactions between the human body and the environment. In particular, the skin microbiome serves as the primary interface with the external environment and aids in host immune function by contributing as the first line of defense against pathogens. Despite these important connections, we have only a basic understanding of how the skin microbiome is first established, or which environmental factors contribute to its development. To this end, this study compared the skin bacterial communities of infants (n?=?47) living in four populations in Mexico and the United States that span the socioeconomic gradient, where we predicted that variation in physical and social environments would shape the infant skin microbiome. Results of 16S rRNA bacterial gene sequencing on 119 samples (armpit, hand, and forehead) showed that infant skin bacterial diversity and composition are shaped by population-level factors, including those related to socioeconomic status and household composition, and vary by skin site and infant age. Differences in infant-environment interactions, including with other people, appear to vary across the populations, likely influencing infant microbial exposures and, in turn, the composition of infant skin bacterial communities. These findings suggest that variation in microbial exposures stemming from the local environment in infancy can impact the establishment of the skin microbiome across body sites, with implications for developmental and health outcomes.IMPORTANCE This study contributes to the sparse literature on the infant skin microbiome in general, and the virtually nonexistent literature on the infant skin microbiome in a field setting. While microbiome research often addresses patterns at a national scale, this study addresses the influence of population-level factors, such as maternal socioeconomic status and contact with caregivers, on infant skin bacterial communities. This approach strengthens our understanding of how local variables influence the infant skin microbiome, and paves the way for additional studies to combine biological sample collection with questionnaires to adequately capture how specific behaviors dictate infant microbial exposures. Work in this realm has implications for infant care and health, as well as for investigating how the microbial communities of different body sites develop over time, with applications to specific health outcomes associated with the skin microbiome (e.g., immune system development or atopic dermatitis).