Abstract <p>Sugarcane molasses is a byproduct of the sugar industry. Its low cost and high remnant sugar content make it an ideal carbon source for bioethanol fermentation using the yeast <i>Saccharomyces cerevisiae</i> as a brewer. After long-term domestication, industrial <i>S. cerevisiae</i> became strongly adaptable to sugarcane molasses. To understand the related underlying mechanisms, we sequenced and analyzed the whole genome of the sugarcane-isolated diploid industrial <i>S. cerevisiae</i> A1015 strain. Compared to the S288c strain and two other wild isolates collected from the same environment, we observed that the A1015 strain possesses several specific genomic characteristics such as high heterozygous nucleotide variations (including single nucleotide polymorphisms and insertion/deletions). This result indicates that uneven distribution across all chromosomes appears through the outcrossing of compatible lineages and asexual reproduction-resulted relevant heterozygosity loss. In addition, we revealed a pericentric inversion caused by microhomology-mediated end joining in chromosome 16, potentially involving the positive selection of the <i>SSU1</i> gene in ORF/promoter. The presence of genes such as the biotin prototrophic biosynthesis genes <i>BIO1</i> and <i>BIO6</i> or molasses toxicity resistance-related gene <i>RTM1</i>, as well as two copies of invertases, etc. reveals a phenotypic impact on industrial fermentation. Moreover, we identified numerous truncated ORFs in A1015 strain caused by non-triple insertions from tandem duplications, suggesting a unique genome evolution in the present industrial strain for molasses. Taken together, this study helps better understanding the genomic evolution of industrial <i>S. cerevisiae</i> for molasses fermentation.</p>