Importance Individuals diagnosed with cancer have elevated suicide risks compared with the general population. National estimates of suicide risks among individuals with cancer are lacking in the US, and knowledge about risk factors is limited. Objective To provide contemporary estimates of suicide risks associated with cancer and to identify sociodemographic and clinical factors associated with suicide risks among individuals diagnosed with cancer. Design, Setting, and Participants A population-based cohort of individuals diagnosed with cancer from January 1, 2000, to December 31, 2016, from 43 states in the US were followed up through December 31, 2016. Standardized mortality ratios (SMRs) were calculated adjusting for attained age at death, sex, and race and ethnicity groups to compare suicide risks in the cancer cohort vs the general US population. Cox proportional hazards regression models were fitted to identify cancer-specific risk factors of suicide among the cancer cohort. Analyses were conducted from October 27, 2020, to May 13, 2022. Main Outcomes and Measures The main outcomes were risk of suicide death compared with the general population, measured by the standardized mortality ratio; and risk of suicide death associated with sociodemographic and clinical factors among individuals with cancer. Exposure Diagnosis of cancer. Results Among a total of 16 771 397 individuals with cancer, 8 536 814 (50.9%) were 65 years or older at cancer diagnosis, 8 645 631 (51.5%) were male, 13 149 273 (78.4%) were non-Hispanic White, and 20 792 (0.1%) died from suicide. The overall SMR for suicide was 1.26 (95% CI, 1.24-1.28), with a decreasing trend (from an SMR of 1.67 [95% CI, 1.47-1.88] in 2000 to 1.16 [95% CI, 1.11-1.21] in 2016). Compared with the general population, elevated suicide risks were observed in the cancer cohort across all sociodemographic groups, with particularly high SMRs among Hispanic individuals (SMR, 1.48; 95% CI, 1.38-1.58), Medicaid-insured individuals (SMR, 1.72; 95% CI, 1.61-1.84), Medicare-insured individuals 64 years or younger (SMR, 1.94; 95% CI, 1.80-2.07), or uninsured individuals (SMR, 1.66; 95% CI, 1.53-1.80). Moreover, the highest SMR was observed in the first 6 months after the cancer diagnosis (SMR, 7.19; 95% CI, 6.97-7.41). Among individuals diagnosed with cancer, relatively higher suicide risks (ie, hazard ratios) were observed for cancer types with a poor prognosis and high symptom burden in the first 2 years after diagnosis, including cancers of oral cavity and pharynx, esophagus, stomach, brain and other nervous system, pancreas, and lung. After 2 years, individuals with cancers subject to long-term quality-of-life impairments, such as oral cavity and pharynx, leukemia, female breast, uterine, and bladder, had higher suicide risks. Conclusions and Relevance In this cohort study of individuals with cancer, elevated suicide risks remained despite a decreasing trend during the past 2 decades. Suicide risks varied by sociodemographic and clinical factors. Timely symptom management and targeted psychosocial interventions are warranted for suicide prevention in individuals diagnosed with cancer.