Depression-associated cognitive impairments are among the most prevalent and persistent symptoms during remission from a depressive episode and a major risk factor for relapse. Consequently, development of antidepressant drugs, which also alleviate cognitive impairments, is vital. One such potential antidepressant is vortioxetine that has been postulated to exhibit both antidepressant and pro-cognitive effects. Hence, we tested vortioxetine for combined antidepressant and pro-cognitive effects in male Long-Evans rats exposed to the chronic mild stress (CMS) paradigm. This well-established CMS paradigm evokes cognitive deficits in addition to anhedonia, a core symptom of depression. Learning and memory performance was assessed in the translational touchscreen version of the paired-associates learning task. To identify the mechanistic underpinning of the neurobehavioural results, transcriptional profiling of genes involved in the stress response, neuronal plasticity and genes of broad relevance in neuropsychiatric pathologies were assessed. Vortioxetine substantially relieved the anhedonic-like state in the CMS rats and promoted acquisition of the cognitive test independent of hedonic phenotype, potentially due to an altered cognitive strategy. Minor alterations in gene expression profiling in prefrontal cortex and hippocampus were found. In summary, our findings suggest that vortioxetine exhibits an antidepressant effect as well as behavioural changes in a translational learning task.