Abstract Microbial exposures during infancy shape the development of the microbiome, the collection of microbes living in and on the body, which in turn directs immune system training. Newborns acquire a substantial quantity of microbes during birth and throughout infancy via exposure to microbes in the physical and social environment. Alterations to early life microbial environments may give rise to mismatches, where environmental, cultural, and behavioral changes that outpace the body’s adaptive responses can lead to adverse health outcomes, particularly those related to microbiome development and immune system regulation. This study explored the development of the skin microbiome among infants born in Chicago, USA. We collected skin swab microbiome samples from 22 mother-infant dyads during the first 48 hours of life and again at six weeks postpartum. Mothers provided information about social environments and hygiene behaviors that may impact infants’ microbial exposures. Analysis of 16S rRNA bacterial gene sequencing data revealed correlations between infant skin bacterial abundance shortly after birth and factors such as antibiotic exposure and receiving a bath in the hospital. The composition of the infant microbiome at six weeks of age was associated with interactions with caregivers and infant feeding practices. We also found shifts in maternal skin microbiomes that may reflect increased hygiene practices in the hospital. Our data suggest that factors related to the birth and household environment can impact the development of infant skin microbiomes and point to practices that may produce mismatches for the infant microbiome and immune system.