Aqueous Chromolaena odorata leaf extracts enhanced rice seed germination and seedling growth. Five extract concentrations (1, 2, 3, 4, and 5%, w/v) applied as seed soaking and foliar spraying were tested for their disease-reducing effects against rice bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae. For foliar sparying, the extracts were applied using three different methods, i.e., at 7 days before inoculation, at 14 days before inoculation and their combination. It was efficient to apply the 3% extract by seed soaking and foliar spraying at 14 days before inoculation to control BLB as it was the lowest concentration where the disease-reducing effects were observed until 21 DAI. The effects involved induced resistance. Indeed, activities of the four defense-related and antioxidant enzymes, i.e., peroxidase (POX), catalase (CAT), polyphenol oxidase (PPO), and phenylalanine ammonia lyase (PAL), increased after extract application and reached higher levels with both extract application and pathogen inoculation. Activities of POX and CAT were induced earlier and stronger using seed soaking than foliar spraying while those of PPO and PAL increased earlier using foliar spraying than seed soaking. This suggests a combination of both application methods to obtain coordinate increases in activities of the four defense-related and antioxidant enzymes which could provide sufficiently protection to rice plants again the disease.