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Land-use land-cover (LULC) changes are one of the major threats to biodiversity worldwide, since their principal consequences are the loss, fragmentation or degradation of the habitat available for most species. Therefore, in order to provide guidelines for environmental management at the regional scale and thus reverse the trend in degradation, transformations of natural remnants into anthropogenic land uses must be identified and quantified. This study examines LULC transitions from 1987 to 2001 and from 2001 to 2009 in two adjacent watersheds located in the Espinal, one of the least protected ecoregions of Argentina. We detected a 20% loss in ecosystems for the period analyzed and, in particular, 60% of native forests were lost. Changes were mainly driven by the expansion of croplands, which directly transformed wetlands and also acted as an underlying cause of the displacement of ranching activities, which in turn replaced Espinal forests. We developed a conceptual model of observed LULC changes for the study area, which we then complemented by proposing an alternative scenario that reconciles agriculture and biodiversity conservation. These results have implications for provincial land use planning and could contribute to the participatory processes demanded by the recent national legislation sanctioned for the protection of native forests.