Cross‐presentation is an important mechanism by which DCs present exogenous antigens on MHC‐I molecules, and activate CD8⁺ T cells, cells that are crucial for the elimination of tumors. We investigated the feasibility of exploiting the capacity of the mannose receptor (MR) to improve both cross‐presentation of tumor antigens and Th polarization, processes that are pivotal for the anti‐tumor potency of cytotoxic T cells. To this end, we selected two glycan ligands of the MR, 3‐sulfo‐Lewis^A and tri‐GlcNAc (N‐acetylglucosamine), to conjugate to the model antigen OVA and assessed in vitro the effect on antigen presentation and Th differentiation. Our results demonstrate that conjugation of either 3‐sulfo‐Lewis^A or tri‐GlcNAc specifically directs antigen to the MR. Both neo‐glycoconjugates showed, even at low doses, improved uptake as compared with native OVA, resulting in enhanced cross‐presentation. Using MR^−/− and MyD88‐TRIFF^−/− bone marrow‐derived DCs (BMDCs), we show that the cross‐presentation of the neo‐glycoconjugates is dependent on MR and independent of TLR‐mediated signaling. Whereas proliferation of antigen‐specific CD4⁺ T cells was unchanged, stimulation with neo‐glycoconjugate‐loaded DCs enhanced the generation of IFN‐γ‐producing T cells. We conclude that modification of antigen with either 3‐sulfo‐Lewis^A or tri‐GlcNAc enhances cross‐presentation and permits Th1 skewing, through specific targeting of the MR, which may be beneficial for DC‐based vaccination strategies to treat cancer.