Introduction: The benefits of exclusive breastfeeding (EBF) are widely reported. However, it is crucial to examine potential disparities in EBF practices across different regions of a country. Our study uses Tanzania demographic and health survey data to report on the trends of EBF across regions from 1999 to 2016, the patterns of the practice based on geographical location and socioeconomic status, and explores its determinants across the years. Methods: Descriptive statistics were used to establish the trends of EBF by geographical location and wealth quintile. A generalized linear mixed model was developed to incorporate both infant and maternal attributes as fixed covariates while considering enumeration areas and regions as clusters. The fitted model facilitated the estimation of EBF proportions at a regional level and identified key determinants influencing EBF practices across the survey periods. Moreover, we designed breastfeeding maps, visually depicting the performance of different regions throughout the surveys. Results: Across the various survey rounds, a notable regional variation in EBF practices was observed, with coastal regions generally exhibiting lower adherence to the practice. There was a linear trend between EBF and geographical residence (p < 0.05) and socioeconomic standing (p < 0.05) across the survey periods. Rural-dwelling women and those from the least affluent backgrounds consistently showcased a higher proportion of EBF. The prevalence of EBF declined as infants aged (p < 0.001), a trend consistent across all survey waves. The associations between maternal attributes and EBF practices displayed temporal variations. Furthermore, a correlation between exclusive breastfeeding and attributes linked to both regional disparities and enumeration areas was observed. The intra-cluster correlation ranged from 18% to 41.5% at the regional level and from 40% to 58.5% at the enumeration area level. Conclusions: While Tanzania's progress in EBF practices is laudable, regional disparities persist, demanding targeted interventions. Sustaining achievements while addressing wealth-based disparities and the decline in EBF with infant age is vital. The study highlights the need for broad national strategies and localized investigations to understand and enhance EBF practices across different regions and socioeconomic contexts.