Inhibiting the androgen receptor (AR), a ligand-activated transcription factor, with androgen deprivation therapy is a standard-of-care treatment for metastatic prostate cancer (PCa). However, this therapeutic strategy is never curative, with all patients eventually relapsing with lethal castration-resistant prostate cancer (CRPC). Paradoxically, recent studies have suggested that “extreme” activation of AR using high doses of androgens, similarly to suppression of AR activity, can also inhibit the growth of CRPC. This study aimed to investigate the mechanisms underlying CRPC growth suppression in response to high doses of a potent androgen, methyltestosterone (MeT). MeT potently suppressed the growth of PCa cells expressing AR, but not AR-negative models. By integrating ChIP-seq and RNA-seq data, we found that MeT-activated AR resulted in upregulation of genes associated with differentiation and downregulation of genes that promote cell proliferation, DNA replication, and DNA damage responses. Interestingly, the RNA-seq data revealed that MeT also caused increased expression of repetitive elements in the genome, including endogenous retroviruses (ERVs), resulting in double-stranded RNA formation. Mechanistically, increased expression of ERVs was linked to MeT-mediated remodelling of the epigenome, characterised by loss of DNA methylation and re-distribution of the histone modification H3K27me3. ERVs and dsRNAs induced by MeT elicited a viral mimicry response characterised by activation of interferon signalling and upregulation of MHC Class I. Collectively, our study reveals a novel outcome of potent androgenic action in PCa and suggests that manipulating AR activity could be a strategy to sensitize PCa to immunotherapies.