Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder caused by loss of function mutations in the dystrophin (DMD) gene. Phenotypic variability in severity, disease progression, and response to treatment have been observed that are not completely correlated with the underlying genotype, raising the possibility of epigenetic modification. Methylation profiles have been associated with Mendelian neurodevelopmental disorders, and more recently to neuromuscular disorders including DMD. We hypothesized that DNA methylation profiles may provide a link between divergent genotype and phenotypic presentation, as well as offering insights into the molecular mechanisms of variability in DMD. We used Nanopore long read whole genome sequencing (LR-WGS) to interrogate methylation changes. We examined patterns of differential methylation between muscle and saliva samples in DMD affected humans, compared methylation profiles in saliva/blood samples from affected and unaffected humans, and investigated methylation patterns in muscle and blood in mouse models of DMD. We identified differential methylation among individual genes as well as genome wide trends, and evaluated skewed patterns of X-inactivation and phasing based on a single sample rather than a family trio. Our analyses demonstrate the utility of nanopore LR-WGS in identifying methylation profiles using a single laboratory protocol, and provide insight into the molecular mechanisms that may underlie disease severity and progression.