Household water contamination at point of use depends on human, animal and environmental factors embodying all aspects of a One Health approach. This study investigated the association between household factors, the presence of thermotolerant coliform, and the presence of antibiotic resistant bacteria in drinking water among 314 households with children under 5 in Cajamarca, Peru. This study analysed data from a baseline sampling of a randomized controlled trial, including household surveys covering household water management and factors such as household animals, as well as microbiological data from samples collected from drinking water. Data were analysed using generalized linear models. Drinking water samples collected from narrow-mouthed containers were less likely to be contaminated than samples collected from the faucet (OR=0.55, p=0.030) or wide mouthed containers. The presence of thermotolerant coliform was associated with owning farm birds, which increased the proportion of contamination from 42.2% to 59.1% (OR=1.98, p=0.017) and with animal waste observed in the kitchen area, which increased the prevalence of contamination from 51.4% to 65.6% (OR=1.80, p=0.024). Resistance to any antibiotic was higher among pig owners at 60%, relative to non-pig owners at 36.4% (OR=1.97, p=0.012) as well as households with free-roaming animals in the kitchen area at 59.6% compared to households without free-roaming animals at 39.7% (OR=2.24, p=0.035). Recent child antibiotic use increased the prevalence of trimethoprim-sulfamethoxazole resistance among E. coli isolates to 22.3% relative to 16.7% (OR=3.00, p=0.037). Overall, these findings suggest that water storage in a secure container to protect from in-home contamination is likely to be important in providing safe drinking water at point of use. In addition, transmission of thermotolerant coliform and AMR between domestic animals and human drinking water supplies is likely. Further research should explore transmission pathways and methods to support safe drinking water access in multi-species households.