Domestic animal husbandry, a common practice globally, can lead to zoonotic transmission of enteric pathogens. However, this risk has received little attention to date. This systematic review and meta-analysis examines the evidence for an association between domestic exposure to food-producing animals and cases of human diarrhea and specific enteric infections. We performed a systematic review of available literature to examine domestic livestock and poultry as risk factors for diarrhea and applied pre-determined quality criteria. Where possible, we carried out meta-analysis of specific animal-pathogen pairs. We found consistent evidence of a positive association between exposure to domestic food-producing animals and diarrheal illness across a range of animal exposures and enteric pathogens. Out of 29 studies included in the review, 20 (69.0%) reported a positive association between domestic animal exposure and diarrhea. Domestic exposure to poultry revealed a substantial association with human campylobacteriosis (OR 2.73, 95% CI 1.90-3.93). Our results suggest that domestic poultry and livestock exposures are associated with diarrheal illness in humans. Failure to ascertain the microbial cause of disease may mask this effect. Exposure to domestic animals should be considered a risk factor for human diarrheal illness and additional studies may identify potential mitigation strategies to address this risk.