This paper develops the life-sustenance hypothesis to explain the multifaceted phenomenon of the human-nature connection. It is based on an interpretation of Jean-Jacques Rousseau’s philosophy brought into contemporary times via recent multidisciplinary research and theoretical underpinnings. Rousseau suggested that humans have two innate, instinctive drives he called amour-de-soi and pitié—a self-preservative drive, and its enlargement, an inclination to help other living beings in distress. The life-sustenance hypothesis is rooted in a systems biological framework situating humans as interconnected parts within a nested system of life. Corresponding to Rousseau’s drives, this interconnectedness is suggested to give rise to the dynamics between two life-preserving orientations that guide our manners-of-being in the world: a self-sustaining and a ‘life-sustaining’ orientation shared by all organisms, albeit manifested differently. The experience of nature connectedness, along with altruistic impulses, are proposed to be human manifestations of the life-sustaining orientation. Moreover, in line with Rousseau’s philosophy, it is posited that the modern, individualistic lifestyle has given rise to an imbalance between these orientations leading to problems in prosociality, proenvironmentalism, and overall well-being. One means by which to regain balanced manners-of-being might be to enhance our nature connectedness. Possible physiological indicators for the hypothesis are explored.