Aim: This large-scale lesion-symptom mapping study aimed to investigate the necessary neuro-anatomical substrates of 5 cognitive domains frequently affected post stroke: Language, Attention, Praxis, Number, and Memory. This study aims to demonstrate the validity of using routine clinical brain imaging from a large, real-world patient cohort for lesion-symptom mapping. Methods: Behavioural cognitive screening data from the Oxford Cognitive Screen (OCS) and routine clinical neuroimaging from 573 patients was used in voxel-based lesion-symptom mapping analyses. Patients were classed as impaired or not on each of the OCS subtests within cognitive domains of Language, Number, Memory, Visuospatial abilities, Praxis and Executive Attention. Results: Distinct patterns of lesion damage were associated with different domains. Language functions were associated with damage to left hemisphere fronto-temporal areas. Visuo-spatial were associated with damage to posterior occipital areas (Visual Field) and the right temporo-parietal region (Visual Neglect). Different memory impairments were linked to distinct voxel clusters within the left insular and opercular cortices. Deficits which were not associated with localised voxels (e.g. praxis, executive function) represent distributed functions. Conclusion: The standardised, brief Oxford Cognitive Screen was able to reliably differentiate distinct neural correlates critically involved in supporting domain-specific cognitive abilities. By demonstrating and replicating known brain anatomy correlates within real-life clinical cohorts using routine CT scans, we open up VLSM techniques to a wealth of clinically relevant studies which can capitalise on using existing clinical brain imaging.