This study aims at assessing the determinants of microbiological contamination of household drinking water under multiple-use water systems in rural areas of Ethiopia. For this analysis, a random sample of 454 households was surveyed between February and March 2014, and water samples from community sources and household storage containers were collected and tested for fecal contamination. The number of Escherichia coli (E. coli) colony-forming units per 100 mL water was used as an indicator of fecal contamination. The microbiological tests demonstrated that 58% of household stored water samples and 38% of protected community water sources were contaminated with E. coli. Moreover, most improved water sources often considered to provide safe water showed the presence of E. coli. The result shows that households' stored water collected from unprotected wells/springs had higher levels of E. coli than stored water from alternative sources. Distance to water sources and water collection containers are also strongly associated with stored water quality. To ensure the quality of stored water, the study suggests that there is a need to promote water safety from the point-of-source to point-of-use, with due considerations for the linkages between water and agriculture to advance the Sustainable Development Goal 6 of ensuring access to clean water for everyone.