Mobilization of the T cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to optimally harness antigen presenting cells to achieve an effective anti-tumor T cell response. In this study, we show that anti-CD47 antibody-mediated phagocytosis of cancer by macrophages can initiate an anti-tumor T cell immune response. Using the ovalbumin model antigen system, anti-CD47 antibody-mediated phagocytosis of cancer cells by macrophages resulted in increased priming of OT-I T cells (CD8+), but did not prime OT-II T cells (CD4+). The CD4+ T cell response was characterized by a reduction in Foxp3+ regulatory T cells. Macrophages following anti-CD47-mediated phagocytosis primed CD8+ T cells to exhibit cytotoxic effector function in vivo, protecting animals from tumor challenge. We conclude that anti-CD47 antibody treatment not only enables macrophage phagocytosis of cancer, but can also initiate an anti-tumor cytotoxic T cell immune response. Anti-CD47-mediated phagocytosis of cancer cells by macrophages leads to priming of a predominant CD8+ T cell response without priming of CD4+ T cells, demonstrating differential priming of T cell responses by macrophages. Priming of effector CD8+ T cells is difficult to achieve with existing vaccines for cancer and infectious diseases. Anti-CD47-based vaccination strategies serve as a promising new strategy for overcoming this challenge for treating or preventing human disease.