During spermiogenesis, extensive histone modifications take place in developing haploid spermatids besides morphological alterations of the genetic material to form compact nuclei. Better understanding on the overall transcriptional dynamics and preferences of histones and enzymes involved in histone modifications may provide valuable information to dissect the epigenetic characteristics and unique chromatin status during spermiogenesis. Using single-cell RNA-Sequencing, the expression dynamics of histone variants, writers, erasers, and readers of histone acetylation and methylation, as well as histone phosphorylation, ubiquitination, and chaperones were assessed through transcriptome profiling during spermiogenesis. This approach provided an unprecedented panoramic perspective of the involving genes in epigenetic modifier/histone variant expression during spermiogenesis. Results reported here revealed the transcriptional ranks of histones, histone modifications, and their readers during spermiogenesis, emphasizing the unique preferences of epigenetic regulation in spermatids. These findings also highlighted the impact of spermatid metabolic preferences on epigenetic modifications. Despite the observed rising trend on transcription levels of all encoding genes and histone variants, the transcriptome profile of genes in histone modifications and their readers displayed a downward expression trend, suggesting that spermatid nuclei condensation is a progressive process that occurred in tandem with a gradual decrease in overall epigenetic activity during spermiogenesis.