<p>The abnormal tumor vasculature can present a barrier to the infiltration of anti-tumor immune cells, which impairs immune surveillance and response to immunotherapy. Here, we show that genetically deleting the epigenetic factor DNA methyltransferase 1 (<i>Dnmt1</i>) in endothelial cells (ECs) reduces angiogenesis while imparting profound changes to the tumor immune microenvironment (TIME), including increased proportions of CD4⁺ memory T cells and NK cells. Depleting CD4⁺ T cells, or blocking lymphocyte egress from the lymph nodes, rescues tumor growth in mice with conditional deletion of <i>Dnmt1</i> in ECs (<i>Dnmt1</i>^iECKO) and dramatically shortens overall survival, whereas NK cells are dispensable. Tumors implanted in <i>Dnmt1</i>^iECKO mice show reduced vascular branching, elevated expression of VCAM1, increased vessel-associated T cells, and a shift in vascular specification, including increased proportions of immune-permissive post-capillary venules (PCVs) and interferon-stimulated ECs (IFN-ECs). Deleting <i>Dnmt1</i> in EC cultures strikingly potentiates responses to combinations of IFNγ and TNFα and, notably, up-regulates important T-cell co-stimulatory molecules for memory CD4⁺ T cells, including <i>Icosl</i>, <i>Cd40</i>, and <i>Tnfsf4</i>. Finally, immune checkpoint blockade (ICB) administered to <i>Dnmt1</i>^iECKO mice with experimental melanoma lung metastasis reduces tumor burden, with some mice showing tumor eradication. Our findings identify endothelial <i>Dnmt1</i> as a key regulator of vascular-mediated anti-tumor immunity, providing a rationale for integrating epigenetic modulation of the vasculature with cancer immunotherapy regimens.</p>