Myasthenia gravis (MG) is a common neuromuscular junction disorder and autoimmune disease mediated by several antibodies. Several studies have shown that genetic factors play an important role in MG pathogenesis. To gain insight into the epigenetic factors affecting MG, we report here genome‐scale DNA methylation profiles of MG. DNA was extracted from eight MG patients and four healthy controls for genome‐wide DNA methylation analysis using the Illumina HumanMethylation 850K BeadChip. Verification of pyrosequencing was conducted based on differential methylation positions. Subsequently, C2C12 and HT22 cell lines (derived from mouse) were treated with demethylation drugs. Transcribed mRNA of the screened differential genes was detected using quantitative real‐time PCR. The control and MG group were compared, and two key probe positions were selected. The corresponding genes wereCAMK1DandCREB5(P< 0.05). Similarly, the myasthenic crisis (MC) and non‐MC group were compared and four key probe positions were selected. The corresponding genes wereSAV1, STK3, YAP1, andWWTR1(P< 0.05). Subsequently, pyrosequencing was performed for verification, revealing that hypomethylation of CAMK1D was significantly different between the MG and control group (P< 0.001). Moreover, transcription ofCREB5, PKD, YAP1, andSTK3genes in the C2C12 cells was downregulated (P< 0.05) after drug treatment, but onlyYAP1mRNA was downregulated in HT22 cells (P< 0.05). This is the first study to investigate genome‐scale DNA methylation profiles of MG using 850 K BeadChip. The identified molecular markers of methylation may aid in the prevention, diagnosis, treatment, and prognosis of MG.