Disparity mutagenesis, which focuses on the molecular basis of genetic information replication, is central to the disparity evolutionary theory. However, previous evolutionary theories have not fully addressed the molecular basis of replication. As a result, evolutionary simulations often incorrectly “assumed” equal mutation rates for both daughter strands derived from a parent strand, referred to as “parity mutagenesis” in contrast to “disparity mutagenesis.” Multiple simulations have demonstrated that disparity mutagenesis has numerous unanticipated evolutionary benefits compared to parity mutagenesis. Molecular biological experiments have confirmed the imbalance in mutation rates among daughter strands, strengthening the disparity evolutionary theory. This review summarizes the existing studies on the disparity evolutionary theory and explores its future prospects. Furthermore, this report provides a comprehensive overview of the evolution of DNA sequencing technologies that facilitate the identification of disparity mutagenesis.