Freeze-dried black raspberries (BRB) produce chemopreventive effects in a rat model of colon carcinogenesis; however, the mechanisms of inhibition were not determined. Herein, we used two mouse models of human colorectal cancer to determine if dietary BRBs would inhibit colorectal tumor development and to investigate the underlying mechanisms. We found that a 12-week feeding of BRBs significantly inhibited intestinal tumor formation in both models; reducing tumor incidence by 45% and tumor multiplicity by 60% in Apc1638+/- mice and tumor incidence and multiplicity by 50% in Muc2-/- mice. Mechanistic studies revealed that BRBs inhibit tumor development in Apc1638+/- mice by suppressing β-catenin signaling and in Muc2-/- mice by reducing chronic inflammation. Intestinal cell proliferation was inhibited by BRBs in both animal models; however, the extent of mucus cell differentiation was not changed in either model. Collectively, our data suggest that BRBs are highly effective in preventing intestinal tumor development in both Apc1638+/- and Muc2-/- mice through targeting multiple signaling pathways.