For the past decades spaceflight has been a driver for technology development in various fields, e.g. generation of electrical power, and computers. Human spaceflight missions, require resources typically scarce (e.g. oxygen) and are usually transferred along with the crew to the respective mission target. Future long-term missions aim beyond Low Earth Orbit (i.e. Moon and Mars), necessitating advances especially in closed-loop life-support systems to guarantee mission autonomy. This requires careful handling of the resources, i.e. minimizing waste and where possible harvesting resources in situ. Similarly, on Earth a sustainable way of life requires careful handling of resources. This paper discusses how both pathways relate to each other and how “settling” Earth sustainably and settling in any space location do not differ in their basic paradigms. It is shown how spaceflight has had an impact on sustainability in the past, which technologies are developed for human spaceflight and how they can be applied on Earth to improve sustainability. Finally, a research infrastructure is presented, which can conduct research on closed-loop technologies, immediately benefiting space and terrestrial applications. This incubator is divided into separate functional modules, which allow testing of technology components. These components can be exchanged to test various permutations of technologies. It is recommended to exploit synergy effects between activities concerning human spaceflight and sustainability by intertwining and coordinating these actions. The technological improvement driven by spaceflight programs can be used to drive sustainability as well.