Expansion of agricultural lands have shaped Brazilian Cerrado landscapes in recent decades; however, the environmental consequences of these transformations are still poorly assessed. This paper presents a multidisciplinary approach used to assess historical land-use and land-cover (LULC) changes and their impacts on the environment in southeast Mato Grosso State, a region where the Cerrado has been intensively converted into agricultural lands. The methodology encompassed three main stages: (1) quantifying LULC changes using remote sensing data, (2) assessing LULC change impacts on vulnerable lands (e.g. erosion prone areas and wetlands), and (3) summarizing preceding information into key environmental indicators, assessed within the Pressure-State-Response framework (PSR) of the Organization for Economic Co-operation and Development (OECD). The results indicated a drastic landscape transformation in the selected area, which evolved from predominantly vegetated to a consolidated agricultural region. Crops expanded at high rates from 1985 to 1995, occupying the majority of the lands suited for agriculture. In the following decade, crops continued to expand and encroached into fragile environments (e.g. wetlands and more erodible soils). As a result, from 1985 to 2005, the area lost approximately 42% of its natural vegetation and erosion risks increased significantly. Our integration of land-use change information with intrinsic environmental vulnerabilities allowed a deeper understanding of LULC changes consequences and provided environmental indicators. This offered a synoptic view of how LULC changes occurred and how they affected the environment at a landscape scale. Furthermore, the assessment of the indicators using the PSR framework, helped to clarify cause–effect relationships thus furnishing key information of value to decision-makers and future comparisons with other areas.