Cytotoxic CD8+ T cells fighting the uncontrolled growth of tumour cells or chronic viral infections such as HIV often undergo functional impairments known as ‘exhaustion’, a state characterized by compromised effector function and elevated expression of immune checkpoints such as PD-1. Importantly, while therapeutic targeting of checkpoints can re-activate exhausted T cell responses and has revolutionized cancer treatment, this treatment is unable to revert the functional impairments linked to T cell exhaustion constituting a fundamental limitation to utilize the full potential of cytotoxic T cells. By comparing T cell responses to acute and chronic LCMV infections, we identified a critical role for the mammalian target of rapamycin (mTOR) pathway in regulating T cell exhaustion. While polyfunctional T cells responding to acute LCMV were capable of activating mTOR signalling, exhausted T cells in chronic LCMV showed impaired mTOR activity. Inhibition of mTOR signalling in acute infection was accompanied with the acquisition of critical features of T cell exhaustion suggesting a direct correlation between mTOR activity and T cell function. Mechanistically, we identified the mTOR inhibitor Ddit4 to be highly expressed in exhausted T cells. Furthermore, T cell-specific deletion of Ddit4 promoted T cell expansion and function in chronic LCMV. Overall, we have identified Ddit4-mediated mTOR inhibition as a novel regulator of T cell exhaustion that might serve as a promising therapeutic target to functionally re-invigorate exhausted T cells and thus promote immune responses in millions of patients suffering from chronic infections and tumours.