Immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) are an established therapeutic option for a range of tumor types but are less effective in immunologically ‘cold’ tumors. We investigated the chemokines essential for immune cell recruitment and subsequent therapeutic efficacy of these immunotherapies. The chemokines upregulated by dual PD-1/ CTLA-4 blockade in preclinical models of breast cancer/ melanoma were assessed in an unbiased manner using nanosting-based analysis with results confirmed at the protein level confirmed by flow cytometry and cytometric bead array. Blocking/ neutralizing antibodies were used to investigate the requirement for key chemokines/cytokines and immune effector cells. Results were confirmed in patients treated with immune checkpoint inhibitors using single-cell RNAseq datasets. The CXCR3 ligands, CXCL9 and CXCL10, were significantly upregulated following dual PD-1/CTLA-4 blockade and both CD8+T cell infiltration and therapeutic efficacy were CXCR3 dependent. In murine models and patients undergoing immunotherapy macrophages were the predominant source of CXCL9 and their depletion abrogated CD8+ T cell infiltration and the therapeutic efficacy of dual immune checkpoint blockade. Single cell RNA-seq analysis of TILs in patients treated with immune checkpoint blockade revealed that CXCL9/10/11 was predominantly expressed by macrophages and we identified a distinct macrophage signature that correlated with response to immune checkpoint blockade. These data underline the fundamental importance of macrophage-derived CXCR3 ligands in the therapeutic efficacy of immune checkpoint blockade and highlight the potential of manipulating this axis to enhance patient responses to immunotherapy.