Abstract: Watermelon Citrullus lanatus (Thunb.) Matsum and Nakai is an important fruit that is commonly eaten all over the world. However, studies have shown that continuous cropping of watermelon on the same field could lead to serious problems, including poor plant growth, reduced production and low disease resistance called soil sickness. It has also been noted that intercropping or rotating watermelon with wheat, a process known as companion wheat, could reduce soil sickness disease. To further explore companion wheat 'D₁₂₅' effect on the growth of watermelon, pot experiments were conducted to investigate the response of photosynthetic characteristics and disease resistance in watermelon to companion with wheat 'D₁₂₅'. The two treatments were monoculture watermelon (the control) and watermelon in companion with wheat. The tested soil was planted with watermelon for three consecutive years. The results showed that photosynthetic rate, stomatal conductance and intercellular CO₂concentration of watermelon in companion with wheat were significantly higher than those of monoculture watermelon by 32.2%, 28.5% and 7.8%, respectively. Chlorophyll (chl a + chl b, chl a, and chl a/b) contents of watermelon in companion with wheat were also significantly higher than those in monoculture watermelon on the 40th day after transplanting by 7.5%, 8.4% and 3.2%, respectively. Similar results were obtained on the 60th day after transplanting for photosynthetic rate, stomatal conductance, intercellular CO₂ concentration and chlorophyll (chl a + chl b, chl a, and chl a/b) contents of watermelon in companion with wheat, all of which were significantly higher than those in monoculture watermelon by 52.9%, 116.7%, 33.8%, 5.8%, 7.1% and 4.9%, respectively. No significant differences in Fo, Fυ, Fυ/Fm, ФPSⅡ and qP were noted between the two cropping systems. Powdery mildew disease index of watermelon leaf decreased by 6.3% in companion cropping system, compared with monoculture watermelon on the 40^th day after transplanting watermelon. Also compared with monoculture cropping, MDA content and PAL activity of watermelon leaf in companion cropping system decreased by 44.43% and 8.68%, respectively. The activities of SOD and PPO in watermelon leaf increased by 17.3% and 84.5%, respectively. On the 60^th day after transplanting watermelon, PAL activity of watermelon in companion with wheat was higher than that in monoculture watermelon. No significant differences were noted in MDA content and SOD and PPO activities between the two cropping systems. The results of the study suggested that watermelon had a positive response to wheat 'D₁₂₅' as a companion crop. The companion of watermelon with wheat 'D₁₂₅' was also beneficial for improving photosynthetic characters, increasing disease resistance of watermelon under continuous cropping system.