Abstract: Eupatorium adenophorum, the most harmful invasive plant in China, has huge negative impacts on agriculture, forestry, animal husbandry, and the ecological environment in Southwest China. It is important to control the spread of this invasive plant and to utilize the plant residues produced during its elimination. In this study, therefore, fresh E. adenophorum plants were pulled out and composted at the same site, and then the compost was used as an organic fertilizer in combination with chemical fertilizers at different proportions for grape plants cultivated in an orchard. The yield and quality of table grape and selected characteristics of soil (microorganisms, nutrient contents, and enzyme activities) in the orchard were analyzed. The results indicated that there was no significant variation in grape yields among the fertilizer treatments, but there were differences in grape quality. The grapes were larger, heavier, with higher contents of soluble solids and sugars, and a higher sugar/acid ratio in the M₇₅ (25% chemical fertilizer+75% organic fertilizer) treatment than in the chemical fertilizer only treatment. The vitamin C content in grapes increased and the nitrate concentration decreased with increasing amounts of organic fertilizer. Although soils in the M₅₀ (50% chemical fertilizer+50% organic fertilizer) and M₇₅ treatments had similar microbial carbon and nitrogen contents, the microbial carbon content was 23.2% and 29.4% higher, respectively, and the microbial nitrogen content was 17.5% and 20.8% higher, respectively, than those in the chemical fertilizer only treatment. There were more culturable bacteria, fungi, and actinomycetes in soils treated with organic fertilizer than in soils treated with chemical fertilizer only. Furthermore, application of organic fertilizer alleviated soil acidification. The activities of catalase, urease, and invertase in soils varied among grape growth periods and were synchronized with the nutrient requirements of grape plants. Application of organic fertilizer in combination with chemical fertilizer at appropriate proportions stimulated soil enzyme activities. Therefore, E. adenophorum compost had positive effects on grape quality and soil fertility. Composting E. adenophorum plants could be an effective way to turn this harmful weed into a beneficial product and to utilize an abundant resource.