Bacterial leaf spot of tomato caused by Xanthomonas campestris pv. vesicatoria is one of the most destructive biotic stresses that significantly affects the quality and productivity of tomatoes. In the current study, we investigated the effects of ten chemicals, including Score (24.51%), Topsim-M (70%), Cabrio (60%), Fossil (29%), Milvet (80%), Forum Top (53%), Excel (80%), Evcin (80%), Electus Super (30%), and Copper hydroxide (52.4%), as well as ten antibiotics, namely Quinocel (10%), Neflox (30%), Gentam (20%), Velocef (29%), Rithmo (44%), Cefcom (52.4%), Cefstar (52.41%), Novamox-LA (15%), Trisulpha (53%), and Inocef (80%), at different concentrations under laboratory conditions, using the inhibition zone technique. In greenhouse conditions, the most effective chemicals and antibiotics, both individually and in combination, were evaluated at various concentrations against bacterial leaf spot of tomatoes. A Completely Randomized Design was employed for both laboratory and greenhouse experiments. The results from the laboratory conditions indicated that Score exhibited the maximum inhibition zone (34.83 mm), followed by Neflox (29.07 mm) against X. campestris pv. vesicatoria, compared to the control. Disease severity was assessed using a disease rating scale at specific time intervals. The results showed that the combination of Score and Neflox exhibited the least disease severity (7.50%), followed by other treatments.