Significance The transcription factor IRF4 controls activation and differentiation of CD8 ⁺ T cells; however, its role in memory T cells is unclear. Here, we use a mouse model that allows removal of IRF4 from CD8 ⁺ T cells after their activation. We show that IRF4 is differentially required for long-term survival of CD8 ⁺ memory T cell subsets. In particular, maintenance of tissue-resident memory T cells appears to depend on IRF4. Upon reactivation, IRF4-deficient CD8 ⁺ memory T cells are strongly impaired in their proliferation and cytokine response. Thus, IRF4 is essential for the function CD8 ⁺ memory T cells.