Many studies have reported that adherence to health promotion guidelines for diet, physical activity, and maintenance of healthy body weight may decrease cancer incidence and mortality. A systematic review was performed to examine associations between adherence to established cancer prevention guidelines for diet and physical activity and overall cancer incidence and mortality. PubMed, Google Scholar, and Cochrane Reviews databases were searched following the current recommendations of Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Twelve studies met inclusion criteria for this review. High versus low adherence to established nutrition and physical activity cancer prevention guidelines was consistently and significantly associated with decreases of 10% to 61% in overall cancer incidence and mortality. Consistent significant reductions were also shown for breast cancer incidence (19%-60%), endometrial cancer incidence (23%-60%), and colorectal cancer incidence in both men and women (27%-52%). Findings for lung cancer incidence were equivocal, and no significant relationships were found between adherence and ovarian or prostate cancers. Adhering to cancer prevention guidelines for diet and physical activity is consistently associated with lower risks of overall cancer incidence and mortality, including for some site-specific cancers. Cancer Epidemiol Biomarkers Prev; 25(7); 1018-28. ©2016 AACR.