Checkpoint blockade immunotherapy (CBI) is a cornerstone of modern cancer treatment, but efficacy is not universal, partly due to a wide variation in baseline immune cell infiltration in the tumor microenvironment (TME). One mechanism contributing to this variability is tumor cell-intrinsic activation of the β-catenin signaling pathway, which has been shown to drive a non-T cell-inflamed TME leading to a loss of therapeutic efficacy of a range of immunotherapies. There is great interest in drugging the Wnt/β-catenin pathway in an effort to restore immune interactions in β-catenin-active tumors. As a proof-of-concept, we reasoned that a genetic experiment eliminating β-catenin expression after establishment of a non-T cell-inflamed TME would illustrate the maximal biologic effect that could be expected with total blockade of the pathway. We developed a genetically engineered mouse (GEM) model that allows for dynamic regulation of β-catenin on and off via doxycycline. We observed that administration of doxycycline resulted in robust nuclear accumulation of melanocyte-specific β-catenin which was accompanied by a reduction in CD3+ T cell infiltration. Discontinuing doxycycline treatment led to loss of nuclear β-catenin expression, associated with a substantial return of CD3+ T cells into the TME. However, despite the re-infiltration of CD3+ T cells, the tumors previously expressing β-catenin did not regain therapeutic responsiveness to anti-CTLA-4 plus anti-PD-L1 therapy. Single cell RNA sequencing of the ex-β-catenin tumors indicated the enrichment of an immunosuppressive-like macrophage population, characterized by the expression of Ccl8, Gas6, Cd163 and Cd209g Moreover, spatial transcriptomic analysis demonstrated that CD3+ T cells are in close contact with these M2-like macrophages, likely resulting in their inhibition. This finding suggests that the prior presence of β-catenin may induce long-lasting changes in the TME that continue to suppress the immune response even after β-catenin levels are reduced, having important therapeutic implications.