Salt stress is one of the main abiotic stresses that affects plant growth and development, as well as crop yield. A large number of studies have reported that the WRKY gene family plays significant roles in the plant responses to salt stress, but the underlying mechanisms remain largely unknown, and research on WRKY proteins in sorghum is also limited. In this study, we identified the sorghum gene SbWRKY51, which encodes a group II WRKY transcription factor. The expression of SbWRKY51 was up-regulated by salt stress, drought, and abscisic acid (ABA) in sorghum. Overexpression of SbWRKY51 via Agrobacterium rhizogenes-mediated hairy root transformation enhanced salt tolerance of sorghum with longer root length, increased biomass accumulation, less Na+ content, and higher antioxidant enzyme activities compared with wild-type (WT) plants. Ectopic expression of SbWRKY51 in Arabidopsis showed similar phenotypes, and mutation of the homologous gene AtWRKY11 increased salt sensitivity of Arabidopsis. Under salt stress, the SbWRKY51-overexpressed transgenic sorghum showed altered expression levels of genes related to oxidative stress and lignin biosynthesis, as well as increased lignin content. Thus, these results suggest that SbWRKY51 positively regulates salt tolerance in sorghum by affecting lignin biosynthesis.