The ancestors of the Equus lived on earth about 55 million years ago, and then they diverged and evolved into modern horses, donkeys and zebras. Equus is indispensable for human lives. Horses are key members of the livestock, domesticated for farming, transportation, recreation as well as food supply and warfare, thereby enhancing the development of human civilization. In the meantime, humans also influence horses’ evolution to meet their own demands, resulting in lots of different horse breeds with specific traits after a prolonged natural and artificial selection. Besides horses, donkeys and mules in the Equus genus also benefit human lives, providing essential work force and also food and nutrition products. The advent of the high-throughput sequencing technologies and bioinformatics analysis has transformed the genetics research of the livestock. In this review, we summarize research progress in the whole genome of Equus by using high-throughput sequencing technologies. Moreover, we describe the achievements on evolution history and functional gene research of Equus using the technology. We look forward to providing further insights for better industrialization and utilization of Equus.