AbstractBacterial wilt is a devastating disease of tomato (Solanum lycopersicum) caused byRalstonia solanacearumthat severely threatens tomato production. Group III WRKY transcription factors (TFs) are implicated in the plant response to pathogen infection; however, their roles in the response of tomato toR. solanacearuminfection (RSI) remain largely unexplored. Here, we report the crucial role of SlWRKY30, a group III SlWRKY TF, in the regulation of tomato response to RSI.SlWRKY30was strongly induced by RSI.SlWRKY30overexpression reduced tomato susceptibility to RSI, and also increased H2O2accumulation and cell necrosis, suggesting that SlWRKY30 positively regulates tomato resistance to RSI. RNA sequencing and reverse transcription–quantitative PCR revealed thatSlWRKY30overexpression significantly upregulated pathogenesis-related protein (SlPR-STH2) genesSlPR­STH2a,SlPR­STH2b,SlPR­STH2c, andSlPR­STH2d(hereafterSlPR­STH2a/b/c/d) in tomato, and theseSlPR-STH2genes were directly targeted by SlWRKY30. Moreover, four group III WRKY proteins (SlWRKY52, SlWRKY59, SlWRKY80, and SlWRKY81) interacted with SlWRKY30, andSlWRKY81silencing increased tomato susceptibility to RSI. Both SlWRKY30 and SlWRKY81 activatedSlPR­STH2a/b/c/dexpression by directly binding to their promoters. Taking these results together, SlWRKY30 and SlWRKY81 synergistically regulate resistance to RSI by activatingSlPR-STH2a/b/c/dexpression in tomato. Our results also highlight the potential ofSlWRKY30to improve tomato resistance to RSI via genetic manipulations.