Studies demonstrate higher mortality rates from colon cancer in American Indian/Alaskan Native (AI/AN) patients compared to non-Hispanic White (nHW). We aim to identify factors that contribute to survival disparities. We used the National Cancer Database to identify AI/AN (n = 2127) and nHW (n = 527,045) patients with stage I-IV colon cancer from 2004 to 2016. Overall survival among stage I-IV colon cancer patients was estimated by Kaplan-Meier analysis; Cox proportional hazard ratios were used to identify independent predictors of survival. AI/AN patients with stage I-III disease had significantly shorter median survival than nHW (73 vs 77months, respectively; p < 0.001); there were no differences in survival for stage IV. Adjusted analyses demonstrated that AI/AN race was an independent predictor of higher overall mortality compared to nHW (HR 1.19, 95% CI 1.01-1.33, p = 0.002). Importantly, compared to nHW, AI/AN were younger, had more comorbidities, had greater rurality, had more left-sided colon cancers, had higher stage but lower grade tumors, were less frequently treated at an academic facility, were more likely to experience a delay in initiation of chemotherapy, and were less likely to receive adjuvant chemotherapy for stage III disease. We found no differences in sex, receipt of surgery, or adequacy of lymph node dissection. We found patient, tumor, and treatment factors that potentially contribute to worse survival rates observed in AI/AN colon cancer patients. Limitations include the heterogeneity of AI/AN patients and the use of overall survival as an endpoint. Additional studies are needed to implement strategies to eliminate disparities.