Objectives: Colorectal cancer (CRC) age-standardized mortality rates (ASMR) are increasing in the North Africa and Middle East (NAME) region, in contrast to the global trend. While the upward trend of the CRC mortality in the NAME region is evident, the key drivers of this increase are still not fully established. We sought to examine the impact of 11 risk factors on the rise in CRC mortality in the region. Methods: We obtained data from the Global Burden of Disease study 1990–2019. We examined changes in risk-related ASMR (ASMRΔ) for high body mass index (BMI), high fasting plasma glucose (FPG), low physical activity, smoking, alcohol, and six dietary factors. Analyses were stratified by sex. Rates and rate differences were expressed per 100 000. Results: CRC ASMR in the NAME region increased by 19.5% (ΔASMR = 1.6). ASMR increased by 25.0% (ΔASMR = 2.1) in men and 16.5% (ΔASMR = 1.3) in women. High FPG and high BMI had the highest risk-attributed ASMRΔ in the NAME population (0.56 and 0.55, respectively). In men, high BMI had the highest risk-attributed ΔASMR (0.85), while in women, high FPG had the highest risk-attributed ΔASMR (0.50). ΔASMR, related to all metabolic risks, (high FPG and high BMI) explained 64.4% of the CRC mortality increase in the region, 63.8% of the increase in men, and 53.8% of the increase in women. Conclusions: CRC mortality is increasing in the NAME region; hyperglycemia and obesity are the key drivers of the increasing trend. Interventions targeting metabolic risks are needed.