Purpose <p>The water resources in California are polluted with nitrate (NO₃) due to the ever-increasing application of nitrogen-based fertilizers. Considering the potential connection between NO₃ in drinking water and the incidence rate of colorectal cancer, this study aims to investigate the association between long-term exposure to NO₃ via drinking water and the incidence of colorectal cancer from 2010 to 2015 in California.</p> Methods <p>A total of 56,631 diagnoses of colorectal cancer were recorded from 2010 to 2015. A generalized linear model was used to obtain the risk ratio (RR) and 95% confidence interval associated with a 1&#xa0;mg/l-NO₃ increase in NO₃ concentration across five latency periods. The potential effect modification by sex, race/ethnicity, and age (&gt; 40, 41–64, 65–90, and &gt; 90) was explored through stratification.</p> Results <p>The association between increases in the concentration of NO₃ at lag 0–1, lag 0–5, lag 0–10, lag 0–15, and lag 0–20 (RRs: 1.056 [1.055, 1.058]; 1.066 [1.063, 1.069]; 1.030 [1.028, 1.031]; 1.017 [1.016, 1.018]; 1.035 [1.034, 1.037], respectively) was positively associated with the RR of colorectal cancer. Sex was not found to be a significant modifier. The RRs for Hispanics, Blacks, and other races were greater than those for Whites; the RRs across different age categories were all significantly positive.</p> Conclusion <p>This study confirms an association between long-term NO₃ exposure in drinking water and the incidence of colorectal cancer in California, emphasizing the need for stringent water quality control and public health strategies to address this risk, particularly in vulnerable populations.</p>