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In Chile, colorectal cancer (CRC) is the fourth cause of death by cancer. Few studies have evaluated the role of contextual and individual socio-economic variables associated with premature death by CRC (<70 years). We analyzed the association between socio-economic factors (at individual and contextual levels) and premature death from CRC in Santiago de Chile. This was a cross-sectional study. We analyzed deaths from CRC between 2014 and 2018 using data published by the Ministry of Health. Individual predictors were sex, marital status, and educational level. Contextual variable included the Social Priority Index (SPI) of the commune where the deceased lived. The association was assessed through multilevel logistic regression models. During the period, 4762 deaths occurred (51.7% women); 39.3% were premature. At the individual level, male sex (odds ratio [OR] 1.36; 95% confidence interval [CI] 1.20–1.53) and single marital status (OR 1.45; 95% CI 1.24–1.68) were associated with premature death from CRC. Primary or lower education was a protective factor (OR 0.53; 95% CI 0.47–0.60). At the contextual level, communes with a higher SPI were three times more at risk than those with a lower SPI (OR 3.13; 95% CI 2.15–4.57). This study showed that individual and contextual socio-economic variables are related to premature death from CRC. Residing in communes with greater socio-economic vulnerability was associated with greater risk. To reduce this gap, it is urgent to design and implement structural policies to reduce social inequities and improve access to health care. [ABSTRACT FROM AUTHOR]