Systemic vasculitides represent a group of autoimmune-autoinflammatory diseases affecting blood vessels. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, emerged as important players in the pathophysiology of systemic vasculitides. Epigenetic dysregulation of key inflammatory and immune-modulating pathways—such as those governing cytokine production, immune cell activation, and endothelial cell survival—is observed across multiple vasculitides. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, the aberrant DNA methylation and histone alterations contribute to expression of autoantigens, while specific micro-RNAs (miRNAs) influence immune cell function, inflammation regulation, and vascular damage. In IgA vasculitis, miRNAs drive immune cell recruitment and endothelial apoptosis, while histone modifications, DNA methylation, and long non-coding RNAs further affect immune response and inflammation. In Kawasaki disease, DNA methylation patterns and non-coding RNAs are linked to immune dysregulation, vascular inflammation, and intravenous immunoglobulin treatment response. In large-vessel vasculitis, epigenetic modifications in genes regulating immune pathways contribute to the vascular remodeling seen in giant cell arteritis and Takayasu arteritis, and miRNAs involved in inflammatory signaling further exacerbate endothelial damage and leukocyte recruitment. Epigenetic research on Behçet’s disease reveals the impact of cytokine gene methylation on immune dysregulation, while miRNA-mediated modulation of the Th17/Treg balance perpetuates the characteristic chronic inflammation.