Background Drinking water at U.S. Marine Corps Base Camp Lejeune, North Carolina was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. Methods A cohort cancer incidence study was conducted of Marines/Navy personnel who, between 1975 and 1985, began service and were stationed at Camp Lejeune, North Carolina (N=154,821) or Camp Pendleton, California (N=163,484), and civilian workers employed at Camp Lejeune (N=6,494) or Camp Pendleton (N=5,797) between October 1972 and December 1985. Camp Pendleton drinking water was not known to be contaminated between 1972 and 1985. Individual-level information on all primary invasive cancers and in-situ bladder cancer diagnosed from 1996 to 2017 was obtained from data linkages with 54 cancer registries in the U.S. Survival methods were used to calculate hazard ratios (HRs) comparing cancer incidence between the Camp Lejeune and Camp Pendleton cohorts. Precision of effect estimates were evaluated using the 95% confidence interval (CI) ratio. Results Cancers among Camp Lejeune Marines/Navy personnel and civilian workers totaled 12,083 (354/100,000) and 1,563 (1,301/100,000), respectively. Cancers among Camp Pendleton Marines/Navy personnel and civilian workers totaled 12,144 (335/100,000) and 1,416 (1,372/100,000), respectively. Compared to Camp Pendleton, Camp Lejeune Marines/Navy personnel had adjusted HRs ≥1.20 with 95% CI ratios (CIRs) ≤3 for acute myeloid leukemia (HR=1.38, 95% CI: 1.03, 1.85), all myeloid cancers including polycythemia vera (HR=1.24, 95% CI:1.03, 1.49), myelodysplastic and myeloproliferative syndromes (HR=1.68, 95% CI: 1.07, 2.62), polycythemia vera alone (HR=1.41, 95% CI: 0.94, 2.11), cancers of the esophagus (HR=1.27, 95% CI: 1.03, 1.56), larynx (HR=1.21, 95% CI: 0.98, 1.50), soft tissue (HR=1.21, 95% CI: 0.92, 1.59) and thyroid (HR=1.22, 95% CI: 1.03, 1.45). Compared to Camp Pendleton, Camp Lejeune civilian workers had adjusted HRs ≥1.20 with 95% CIRs ≤3 for all myeloid cancers including polycythemia vera (HR=1.40, 95% CI: 0.83, 2.36), squamous cell lung cancer (HR=1.63, 95% CI: 1.10, 2.41) and female ductal breast cancer (HR=1.32, 95% CI:1.02, 1.71). Sensitivity analyses indicated that confounding bias due to unmeasured risk factors (e.g., smoking and alcohol consumption) is unlikely to significantly impact the findings. Conclusion Increased risks of several cancers were observed among Marines/Navy personnel and civilian workers likely exposed to contaminated drinking water at Camp Lejeune compared to personnel at Camp Pendleton.