The application of sulfate-reducing bacteria (SRB) shows great potential in the anaerobic biological treatment of acid mine wastewater; therefore, it has attracted much attention. The low pH in acidic wastewater affects the growth and reducing power of SRB. To uncover the mechanism underlying the reduction efficiency of SRB under acidic conditions, in this study, transcriptomic analysis was performed with Desulfovibrio vulgaris ATCC 7757 under three different pH conditions (pH 4.0, 5.5 and 7.0) and in the initial inoculation, logarithmic growth and plateau phases. Our results showed that ATCC 7757 still had biological activity at pH 4.0 and exhibited gene expression patterns at pH 4.0 that were different from those at pH 5.5 and pH 7. Importantly, the gene expression pattern was similar between pH 5.5 and pH 7. Transcriptomic analysis identified differentially expressed genes that affected the growth of ATCC 7757 under pH 7.0 at 22 h compared to 15 h; 196 of these genes were upregulated and 575 were downregulated. These differentially expressed genes were mainly enriched in genetic information processing and metabolism. Additionally, we identified 57 candidate genes associated with low-pH tolerance. Adaptation to low pH was reflected by an increase in the expression of genes involved in cell membrane structure and proton transport. The expression of genes involved in the reduction process decreased, including the genes DVU0499 and sat, which encode proteins that affect the sulfate reduction process. Both gene activities were validated by qPCR. Our results will contribute to further promoting the reducing power of SRB in acid mine wastewater and the development of successful bioremediation strategies.