Using a case-control design, this investigation explored non-genetic determinants of colorectal cancer (CRC) among individuals in South Sulawesi. The participant pool comprised 89 cases and 84 controls, spanning ages 19 to 86, with 99 men and 74 women from multiple ethnicities. Univariate assessments employed chi-square, Fisher’s exact test, t-test, and Mann-Whitney U test. A logit model with L1 regularization, adjusted for age, gender, and ethnicity, pinpointed noteworthy non-genetic risk factors. The variables scrutinized included patient weight, height, body mass index (BMI), site of defecation, physical activity, tobacco use, marital status, occupation, educational attainment, and proximity to the nearest healthcare facility. The odds ratio estimates from the logit model were used to evaluate the relevance of the identified risk factors. The logit model highlighted tobacco use, educational attainment, marital status, proximity to the nearest healthcare facility, and weight as meaningful risk factors. CRC cases exhibited a greater tendency toward lower education (OR = 1.819, 95% CI = 1.354–2.443), residence in distant areas (OR = 1.44, 95% CI = 1.17–1.772), and weight reduction (OR = 1.03, 95% CI = 1.013–1.048). Controls demonstrated a higher likelihood of being non-smokers (OR = 0.325, 95% CI = 0.149–0.707) and unmarried (OR = 0.161, 95% CI = 0.036–0.716). The findings established that additional non-genetic factors—namely, educational attainment, proximity to the nearest healthcare facility, weight, tobacco use, and marital status—also contributed to CRC incidence among the South Sulawesi population. The research underscored the importance of integrating these factors into subsequent, precisely directed CRC prevention efforts.