Introduction: The high prevalence of multiple chronic conditions (MCC), multimorbidity, and frailty may affect treatment and outcomes for older adults with cancer. The goal of this study was to use three conceptually distinct measures of morbidity to examine the association between these measures and mortality. Materials and Methods: Using Medicare claims data linked with the 2012–2016 Ohio Cancer Incidence Surveillance System we identified older adults with incident primary cancer sites of breast, colorectal, lung, or prostate (n = 29,140). We used claims data to identify their Elixhauser comorbidities, Multimorbidity-Weighted Index (MWI), and Claims Frailty Index (CFI) as measures of MCC, multimorbidity, and frailty, respectively. We used Cox proportional hazard models to examine the association between these measures and survival time since diagnosis. Results: Lung cancer patients had the highest levels of MCC, multimorbidity, and frailty. There was a positive association between all three measures and a greater hazard of death after adjusting for age, sex (colorectal and lung only), and stage. Breast cancer patients with 5+ comorbidities had an adjusted hazard ratio (aHR) of 1.63 (95% confidence interval [CI]: 1.38, 1.93), and those with mild frailty had an aHR of 3.38 (95% CI; 2.12, 5.41). The C statistics for breast cancer were 0.79, 0.78, and 0.79 for the MCC, MWI, and CFI respectively. Similarly, lung cancer patients who were moderately or severely frail had an aHR of 1.82 (95% CI: 1.53, 2.18) while prostate cancer patients had an aHR of 3.39 (95% CI: 2.12, 5.41) and colorectal cancer patients had an aHR of 4.51 (95% CI: 3.23, 6.29). Model performance was nearly identical across the MCC, multimorbidity, and frailty models within cancer type. The models performed best for prostate and breast cancer, and notably worse for lung cancer. The frailty models showed the greatest separation in unadjusted survival curves. Discussion: The MCC, multimorbidity, and frailty indices performed similarly well in predicting mortality among a large cohort of older cancer patients. However, there were notable differences by cancer type. This work highlights that although model performance is similar, frailty may serve as a clearer indicator in risk stratification of geriatric oncology patients than simple MCCs or multimorbidity.