BACKGROUND: While the benefits of exclusive breastfeeding are widely acknowledged, it continues to be a rare practice. Determinants of exclusive breastfeeding in Tanzania have been studied; however, the existence and contribution of regional variability to the practice have not been explored. METHODS: Tanzania demographic and health survey data for 2015/2016 were used. Information on infants aged up to 6 months was abstracted. Exclusive breastfeeding was defined using a recall of feeding practices in the past 24 h. Enumeration areas and regions were treated as random effects. Models without random effects were compared with those that incorporated random effects using the Akaike information criterion. The determinants of exclusive breastfeeding were estimated using the generalized linear mixed model with enumeration areas nested within the region. RESULTS: The generalized linear mixed model with an enumeration area nested within a region performed better than other models. The intra-cluster variability at region and enumeration area levels was 3.7 and 24.5%, respectively. The odds of practicing exclusive breastfeeding were lower for older and male infants, for mothers younger than 18, among mothers residing in urban areas, among those who were employed by a family member or someone else, those not assisted by a nurse/midwife, and those who were not counseled on exclusive breastfeeding within 2 days post-delivery. There was no statistical evidence of an association between exclusive breastfeeding practices and the frequency of listening to the radio and watching television. When mapping the proportion of exclusive breastfeeding, a variability of the practice is seen across regions. CONCLUSION: There is room to improve the proportion of those who practice exclusive breastfeeding in Tanzania. Beyond individual and setting factors, this analysis shows that a quarter of the variability in exclusive breastfeeding practices is at the community level. Further studies may explore the causes of variabilities in regional and enumeration area and how it operates. Interventions to protect, promote, and support exclusive breastfeeding in Tanzania may target the environment that shapes the attitude toward exclusive breastfeeding in smaller geographical areas.