Rice bacterial blight and rice bacterial streak are two serious rice diseases and have caused great harm to the production of rice all over the world. To develop an efficient antibacterial agent with a novel target, a series of novel 2-oxo-N-phenylacetamide derivatives containing a dissulfone moiety were synthesized, and their antibacterial activities were evaluated. Among them, compound D 14 exhibited the best antibacterial activities, especially against Xoo and Xoc with EC50 values of 0.63 and 0.79 mg/L, respectively, which were much better than the commercial control of bismerthiazol (BT) (76.59 and 83.35 mg/L, respectively) and thiodiazole copper (TC) (91.72 and 114.00 mg/L, respectively). Meanwhile, compound D 14 can interact with a CRP-like protein (Clp) of Pxo99A and show strong binding activity with Xoo-Clp with a K d value of 0.52 μM, which was far superior to the corresponding K d values of BT (183.94 μM) and TC (222.58 μM). Treatment of D 14 and deletion of the clp gene could significantly reduce the expression of the clp gene and attenuate the virulence of pathogenic bacteria. These results indicated that compound D 14 could be used as a potential novel agricultural bactericide and Clp can be used as a target protein for the control of plant bacterial diseases. This work provided reliable support for developing novel antibacterial agents based on Clp as a target protein.