AbstractChronic back pain (CBP) is heterogenous and identifying sub-groups could improve clinical decision making. Machine learning can build upon prior sub-grouping approaches by using a data-driven approach to overcome clinician subjectivity, however, only binary classification of pain versus no-pain has been attempted to date. In our cross-sectional study, age- and sex-matched participants with CBP (n = 4156) and pain-free controls (n = 14,927) from the UkBioBank were included. We included variables of body mass index, depression, loneliness/social isolation, grip strength, brain grey matter volumes and functional connectivity. We used fuzzy c-means clustering to derive CBP sub-groups and Support Vector Machine (SVM), Naïve Bayes, k-Nearest Neighbour (kNN) and Random Forest classifiers to determine classification accuracy. We showed that two variables (loneliness/social isolation and depression) and five clusters were optimal for creating sub-groups of CBP individuals. Classification accuracy was greater than 95% for when CBP sub-groups were assessed only, while misclassification in CBP sub-groups increased to 35–53% across classifiers when pain-free controls were added. We showed that individuals with CBP could sub-grouped and accurately classified. Future research should optimise variables by including specific spinal, psychosocial and nervous system measures associated with CBP to create more robust sub-groups that are discernible from pain-free controls.