During ageing, different cognitive functions decline at different rates. Additionally, cognitive reserve may influence inter-individual variability in age-related cognitive decline. These complex relationships can be studied by constructing a so-called cognitive connectome and characterising it with advanced graph-theoretical network analyses. This study examined the effect of cognitive reserve on the cognitive connectome across age. A total of 334 cognitively healthy participants were stratified into early middle age (37–50 years; n = 110), late middle age (51–64 years; n = 106), and elderly (65–78 years; n = 118) groups. Within each age group, individuals were subdivided into high and low cognitive reserve. For each subgroup, a cognitive connectome was constructed based on correlations between 47 cognitive variables. Applying graph theory, different global network measures were compared between the groups. Graph-theoretical network analyses revealed that individuals with high cognitive reserve were characterized by a stable cognitive connectome across age groups. High cognitive reserve groups only differed in modularity. In contrast, individuals with low cognitive reserve showed a marked reconfiguration of cognitive connectomes across age groups with differences extending over a variety of network measures including network strength, global efficiency, modularity, and small-worldness. Our results suggest a stabilizing effect of cognitive reserve on the cognitive connectome. Gaining further insights into these findings and underlying mechanisms will contribute to our understanding of age-related cognitive decline and guide the development of strategies to preserve cognitive function in ageing.