We studied the association between multimorbidity, polypharmacy, and mortality in 1,050 older adults (50+) with intellectual disability (ID). Multimorbidity (presence of ≥ 4 chronic health conditions) and polypharmacy (presence ≥ 5 chronic medication prescriptions) were collected at baseline. Multimorbidity included a wide range of disorders, including hearing impairment, thyroid dysfunction, autism, and cancer. Mortality data were collected during a 5-year follow-up period. Cox proportional hazards models were used to determine the independent association between multimorbidity and polypharmacy with survival. Models were adjusted for age, sex, level of ID, and the presence of Down syndrome. We observed that people classified as having multimorbidity or polypharmacy at baseline were 2.60 (95% CI = 1.86–3.66) and 2.32 (95% CI = 1.70–3.16) times more likely to decease during the follow-up period, respectively, independent of age, sex, level of ID, and the presence of Down syndrome. Although slightly attenuated, we found similar hazard ratios if the model for multimorbidity was adjusted for polypharmacy and vice versa. We showed for the first time that multimorbidity and polypharmacy are strong predictors for mortality in people with ID. Awareness and screening of these conditions is important to start existing treatments as soon as possible. Future research is required to develop interventions for older people with ID, aiming to reduce the incidence of polypharmacy and multimorbidity.