Mental representations of space can be generated and communicated with respect to different reference frames and perspectives. The present study investigated the effects of age and individual differences in domain-general executive functions on people’s ability to process spatial relations as expressed in language within different spatial reference frames (SRFs). Healthy adults aged between 18 and 85 completed a novel task involving self-, third-person-, object-, and environment-centered judgements of spatial relations between two objects, as well as standard tests of working memory, inhibition, and mental flexibility. A psychometric evaluation confirmed the test-retest reliability and the convergent and divergent validity of the new task. Results showed that the lifespan trajectories varied depending on the SRF. Processing from a self-centered perspective or an object-centered frame remained intact throughout the adult-lifespan. By contrast, spatial processing from a third-person-centered perspective or within an environment-centered frame declined in late adulthood. Mediation regression models showed that mental flexibility accounted for a significant part of the age-related variance in spatial processing across all allocentric SRFs. The age effects on environment-centered processing were also partially mediated by age-related changes in visuospatial working memory capacity. These findings suggest that at least partially distinct systems are involved in mentally representing space under different SRFs, which are differentially affected by typical aging. Our results also highlight that people’s ability to process spatial relations across different SRFs depends on their capacity to employ domain-general effortful cognitive resources.