Plant activators are agrochemicals that protect plants from a broad range of pathogens by activating the plant immune system. Unlike pesticides, they do not target pathogens; therefore, plant activators provide durable effects that are not overcome by pathogenic microbes. Although certain plant activators have been applied to paddy fields for more than 30 years, the molecular basis of the underlying immune induction are unclear. From the screening of 10,000 diverse chemicals by a high-throughput screening procedure to identify compounds that specifically enhance pathogen-induced cell death in Arabidopsis cultured cells, we identified 7 compounds, which we designated as immune priming chemicals (Imprimatins). These compounds increased disease resistance against pathogenic Pseudomonas bacteria in Arabidopsis plants. Pretreatments increased the accumulation of endogenous salicylic acid (SA) but reduced its metabolite, SA-O-β-D-glucoside (SAG). Imprimatins inhibited the enzymatic activities of 2 SA glucosyltransferases (SAGTs) in vitro at concentrations effective for immune priming. Single and double knockout Arabidopsis plants for both SAGTs consistently exhibited enhanced disease resistance and SA accumulation. Our results demonstrate that the control of the free SA pool through SA-inactivating enzymes can be a useful methodology to confer disease resistance in plants. SAGTs can pave the way for target-based discovery of novel crop protectants.