Water and sanitation have been related to the health of populations, yet, the effects of these factors on the occurrence of chronic conditions (CC) in later life have been least explored. This study examines the association of CC with water and sanitation among older Ghanaians and whether the associations are moderated by gender and residence. Data from the WHO-SAGE Wave 2 comprising of 4735 adults aged ≥ 50 years were analyzed in this study. The primary outcome was CC and the exposures included sources of water, sanitation facilities, and the sharing of sanitation facilities. Generalized logistic regression models estimated the effects of water and sanitation indicators on the occurrence of CC. Overall, 18.8% of the sample reported at least one CC. Compared to men and rural residents, women and urban residents respectively were more likely to report CC (p < 0.001). After full adjustments, logistic regressions showed that the use of unimproved sanitation (OR = 1.732, CI: 1.377–5.418) and sharing of sanitation facilities (OR = 1.624, CI: 1.095–1.320) were associated with higher odds of CC. However, the use of water did not reach significance (p = 0.125). We found a significant interaction effect for type of toilet × gender (OR = 3.498, CI: 1.744–16.442), source of water × residence (OR = 5.935, CI: 1.320–26.685), and type of toilet × residence (OR = 1.998, CI: 1.462–8.642). The use of unimproved sanitation facilities and the sharing of sanitation facilities are associated with the occurrence of CC among older people. Policy and public health interventions targeted at improving the health and well-being of older people should conspicuously include improving access to sanitation services.