Purpose Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer deaths globally. Over the past two decades, young-onset CRC incidence has risen sharply, with a 5% increase in Australians under 50 and a four-fold rise in those under 40 since 2001. Despite this growing burden, the drivers of young-onset adult cancers remain largely unknown. We compared risk factors between young and late-onset CRC, hypothesising that young-onset CRC arises through pathways distinct from late-onset disease. Methodology The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial dataset, comprising ~155,000 US participants including 1217 CRC cases, was analysed. Participants enrolled from 1993 were stratified by age (≤59 versus ≥60 years). Associations of demographic, clinical and behavioural risk factors with colorectal cancer (stratified by age) were computed using multivariable cox regression with the multiplicative interaction of exposures, while reduced rank regression was applied to nutritional risk factors prior to regression analysis. Results Among the ≤59-year cohort, no individual risk factor was independently associated with the risk of CRC. However, the multiplicative effect of hypertension and smoking appeared to be statistically significantly associated with younger-onset CRC (p = 0.047). In contrast, in the ≥60-year cohort, individual (diverticular disease, colon comorbidities, elevated BMI, alcohol intake and hypertension) as well as combinations of risk factors were associated with CRC. Significant dietary interactions appeared exclusively to impact the risk of CRC in the ≥60-year cohort. Conclusion These findings suggest that the drivers of CRC in young individuals may be different from their older counterparts with interaction between risk factors being more likely to play a role compared to individual risk factors. These data suggest the need to re-consider the traditional ways of thinking about CRC risk in the young.