A long-term localization experiment of peanut-sweet potato rotation system was studied to investigate the effect of different types of organic fertilizer on sweet potato yield, soil microbial abundance, and enzyme activities. This study aimed to provide the basis for selecting appropriate organic fertilizers to increase crop yield and improve soil biological characteristics. Five fertilization treatments were selected:(1) CK, no fertilization control; (2) NPK, chemical fertilizers treatment; (3) NPK + SR, chemical fertilizers + straw return treatment; (4) NPK + M, chemical fertilizers + manure treatment; (5) NPK + P, chemical fertilizers + pig manure treatment. The results showed that the yield and aboveground biomass of sweet potato increased significantly under NPK, NPK+SR, NPK+M, and NPK+P treatments compared with CK treatment, while NPK+P treatment had an optimal effect among NPK, NPK+SR, NPK+M, and NPK+P treatments. In comparison with CK treatment, the abundances of bacteria, fungi, diazotrophic, and microorganism associated with soil organic phosphorus transformation decreased significantly under NPK treatment, while NPK+SR, NPK+M, and NPK+P treatment had mitigatory suppression effect on abundance of these microorganisms mentioned above in different degree. The geometric mean of the assayed enzyme activities (GMea) could be used to evaluate the overall activity of soil enzymes to some extent. The GMea decreased significantly under NPK, NPK+SR, and NPK+M treatments compared with CK treatment, whereas NPK+P treatment improved the geometric mean of the assayed enzyme activities. For single enzyme activity, NPK+P treatment significantly reduced soil urease activity compared with CK treatment (P<0.05), however, NPK+P treatment significantly increased acid phosphatase, alkaline phosphatase, and catalase activities, respectively. In addition, the results of principal component and pearson correlation analysis suggested that soil nutrients and soil organic carbon content were significantly positively correlated with yield and aboveground biomass of sweet potato. Soil pH was the main factor that drives the change of soil microbial abundance and soil enzyme activities. Therefore, long-term combined with organic and inorganic fertilization has achieved a good efficiency on increasing sweet potato yield and improving soil biological properties through increasing soil nutrients, organic carbon content as well as influencing soil pH. Among all the fertilization treatments as we selected, chemical fertilizers plus pig manure had the best effect on enriching the soil fertility and improving crop production.