The southeastern Amazon region has been intensively occupied by human settlements over the past three decades. To evaluate the effects of human settlements on land-cover and land-use (LCLU) changes over time in the study site, we evaluated multitemporal Landsat images from the years 1984, 1994, 2004, 2013 and Sentinel to the year 2017. Then, we defined the LCLU classes, and a detailed “from-to” change detection approach based on a geographic object-based image analysis (GEOBIA) was employed to determine the trajectories of the LCLU changes. Three land-cover (forest, montane savanna and water bodies) and three land-use types (pasturelands, mining and urban areas) were mapped. The overall accuracies and kappa values of the classification were higher than 0.91 for each of the classified images. Throughout the change detection period, ~47% (19,320 km2) of the forest was preserved mainly within protected areas, while almost 42% (17,398 km2) of the area was converted from forests to pasturelands. An intrinsic connection between the increase in mining activity and the expansion of urban areas also exists. The direct impacts of mining activities were more significant throughout the montane savanna areas. We concluded that the GEOBIA approach adopted in this study combines the advantages of quality human interpretation and the capacities of quantitative computing.