Through the expansion of human activities, humanity has evolved to become a driving force of global environmental change and influences a substantial and growing part of natural ecosystem trophic interactions and energy flows. However, by constructing and building its own niche, human distance from nature increased remarkably during the last decades due to processes of globalization and urbanization. This increasing disconnect has both material and immaterial consequences for how humans interact and connect with nature. Indeed, many regions across the world have disconnected themselves from the productivity of their regional environment by: (1) accessing biological products from distant places through international trade, and (2) using non-renewable resources from outside the biosphere to boost the productivity of their natural environment. Both mechanisms allow for greater resource use then would be possible otherwise, but also involve complex sustainability challenges and lead to fundamentally different feedbacks between humans and the environment. This dissertation empirically investigates the sustainability of biophysical human-nature connections and disconnections from a social-ecological systems perspective. The results provide new insights and concrete knowledge about biophysical human-nature disconnections and its sustainability implications, including pervasive issues of injustice. Through international trade and reliance on non-renewables, particularly higher-income regions appropriate an unproportional large share of global resources. Moreover, by enabling seemingly unconstrained consumption of resources and simultaneous conservation of regional ecosystems, increasing regional disconnectedness stimulates the misconception of decoupling. Whereas, in fact, the biophysically most disconnected regions exhibit the highest resource footprints and are, therefore, responsible for the largest environmental damages. The increasing biophysical disconnect between humans and nature effectively works to circumvent limitations and self-constraining feedbacks of natural cycles. The circumvention of environmental constraints is a crucial feature of niche construction. Human niche construction refers to the process of modifying natural environments to make them more useful for society. To ease integration of the chapters in this thesis, the framework paper uses human niche construction theory to understand the mechanisms and drivers behind increasing biophysical disconnections. The theory is employed to explain causal relationships and unsustainable trajectories from a holistic perspective. Moreover, as a process-oriented approach, it allows connecting the empirically assessed states of disconnectedness with insights about interventions and change for sustainability. For a sustainability transformation already entered paths of disconnectedness must be reversed to enable a genuine reconnection of human activities to the biosphere and its natural cycles. This thesis highlights the unsustainability of disconnectedness and opens up debate about how knowledge around sustainable human niche construction can be leveraged for a reconnection of humans to nature.