Comorbidities worsen cancer survival but patterns of pre-existing and new onset comorbidities among cancer survivors are unknown. We investigated self-reported and clinically diagnosed comorbidity among cancer survivors in the All-of-Us program's national database. Eight highly prevalent comorbidities were identified using self-reported data from the personal health history (PHH) survey among cancer survivors (n = 20,534) and non-cancer adults (n = 113,628), and validated among cancer survivors (n = 26,978) using data from electronic health records (EHRs). Among 5-year survivors (n = 9,174) documented in EHR, we further estimated the incidence of new-onset comorbidities. The most prevalent comorbidities identified in PHH data were hypertension (40.5%), osteoarthritis (28.4%), depression (28.0%), and obesity (23.2%). EHR data identified pre-existing comorbidities: hypertension (43.3%), osteoarthritis (29.4%), depression (19.4%), and obesity (19.1%). During five-year survival, over 50% cancer survivors developed at least one new comorbidity, and over 25% developed two or more. The onset of new comorbidities showed a sharp increase in the first-year post-diagnosis. Incidence rates varied by age, race and ethnicity. Future research is needed to develop effective strategies to prevent newly onset comorbidities during and after cancer treatment.