Schizophrenia is a complex and debilitating neuropsychiatric disorder that arises from genetic and environmental factors, both of which may be associated with DNA methylation. There remains a growing need to explore profiles of epigenetic dysregulation specific to clinical dimensions of schizophrenia to dissect molecular features of phenotypic heterogeneity in the disorder and inform precision medicine strategies. Here, we comprehensively analysed patterns of DNA methylation in a cohort of 381 individuals with schizophrenia from the Australian Schizophrenia Research Bank with extensive phenotype data available. Epigenetic changes associated with clinical factors were investigated, including cognitive status, age of onset, treatment resistance, Global Assessment of Function scores, and genetic risk for schizophrenia as indexed by polygenic risk scores. Epigenome-wide association studies (EWAS) of these five clinical dimensions identified a total of 662 differentially methylated probes across all traits at a discovery threshold of P < 6.72x10–5, with many residing in genes previously associated with schizophrenia. We further examined how schizophrenia polygenic risk may influence changes in methylation associated with the remaining clinical traits, which revealed an additional 432 probes. Methylation quantitative trait loci (mQTL) signals uncovered in this cohort also exhibited evidence for a shared causal variant with schizophrenia (N =102, posterior probability > 80%) from a recent genome-wide association study. Interestingly, there was evidence for correlation amongst EWAS and mQTL effect size estimates, which was generally strengthened when restricted to mQTLs with evidence for genetic colocalization. We additionally observed negative correlation between EWAS effect size estimates and methylation-associated expression of neighbouring genes. Finally, we constructed epigenetic risk scores utilising EWAS from an independent cohort, which strikingly explained approximately 6% of phenotypic variance amongst clozapine-treated individuals. Our findings collectively provide novel evidence suggesting clinical dimensions of schizophrenia are associated with alteration of DNA methylation which may contribute to phenotypic variation in the disorder.