The dynamics of soil microbial communities are important for plant health and productivity. Soil microbial communities respond differently to fertilization. Organic water soluble fertilizer is an effective soil improver, which can effectively improve soil nutrient status and adjust soil pH value. However, little is known about the effects of water soluble fertilizers on soil microbial community, and the combined effects on soil nutrients and sugarcane productivity. Therefore, this study sought to assess the effects of water soluble fertilizer (1,050 kg/hm2 (WS1), 1,650 kg/hm2 (WS2)) and mineral fertilizer (1,500 kg/hm2 (CK)) on the soil microbial community, soil nutrients and crop yield of sugarcane. The results showed that compared with CK, the application of water soluble fertilizers (WS1 and WS2) alleviated soil acidity, increased the OM, DOC, and AK contents in the soil, and further improved agronomic parameters and sugarcane yield. Both WS1 and WS2 treatments significantly increased the species richness of microorganisms, especially the enrichment of beneficial symbiotic bacteria such as Acidobacteria and Planctomycetes, which are more conducive to the healthy growth of plants. Furthermore, we found that soil nutrient contents were associated with soil microbial enrichment. These results indicate that water soluble fertilizer affects the enrichment of microorganisms by improving the nutrient content of the soil, thereby affecting the growth and yield of sugarcane. These findings therefore suggest that the utilization of water soluble fertilizer is an effective agriculture approach to improve soil fertility.