Deforestation is a problem that adversely affects the socioeconomic and ecological dimensions of human life locally, nationally and globally. This paper reports on the analysis of the spatial relationships between deforestation (study period: 1995–2010) and protected areas, accessibility, human population density, regional gross domestic product (GDP) and geographic and climatic factors using land use/land cover maps covering the whole of mainland Tanzania. Multiple linear regression analysis was used for statistical analysis of the relationship between deforestation and the explanatory variables. Deforestation was estimated at the rate of 320,067 ha/yr. High deforestation was associated with unprotected areas, low distance to railway, road and town, high population density and high regional GDP. These results have at least the following four implications: (1) Protected areas are better in controlling deforestation than if there were none. (2) Town dwellers depend on forests for wood and livelihood. (3) Roads and railways are not used only to access off farm activities but also to access forests for exploitation and conversion to other land covers than forest. (4) High population density and high GDP did not result in switching from dependence on forests for wood and livelihoods. It is recommended that appropriate strategies should address these implications so that the patterns of dependence on forests for wood and livelihoods are redressed.