Humans are biophysically connected to the biosphere through the flows of materials and energy appropriated from ecosystems. While this connection is fundamental for human well-being, many modern societies have-for better or worse-disconnected themselves from the natural productivity of their immediate regional environment. In this paper, we conceptualize the biophysical human-nature connectedness of land use systems at regional scales. We distinguish two mechanisms by which primordial connectedness of people to regional ecosystems has been circumvented via the use of external inputs. First, 'biospheric disconnection' refers to people drawing on non-renewable minerals from outside the biosphere (e.g. fossils, metals and other minerals). Second, 'spatial disconnection' arises from the imports and exports of biomass products and imported mineral resources used to extract and process ecological goods. Both mechanisms allow for greater regional resource use than would be possible otherwise, but both pose challenges for sustainability, for example, through waste generation, depletion of non-renewable resources and environmental burden shifting to distant regions. In contrast, biophysically reconnected land use systems may provide renewed opportunities for inhabitants to develop an awareness of their impacts and fundamental reliance on ecosystems. To better understand the causes, consequences, and possible remedies related to biophysical disconnectedness, new quantitative methods to assess the extent of regional biophysical human-nature connectedness are needed. To this end, we propose a new methodological framework that can be applied to assess biophysical human-nature connectedness in any region of the world.