Continuous cropping affects the yield and quality of potatoes. In order to reveal the potential mechanism of potato continuous cropping obstacles in southern China, we set up a serial experiments in this study to investigate the effects of potato continuous cropping on soil physical and chemical properties, microbial biomass and enzyme activities. The results showed that the potato planted in newly reclaimed soil yielded in 43.69 t/hm2 without showing common scab symptoms of tubers. The potato yield in continuous cropping soil was significantly reduced to 25.63 t/hm2 with the scab symptoms on tubers, accounting for 6.7%. After planting potatoes for one season in spring, the soil pH decreased, while the available phosphorus, total phosphorus, total nitrogen, alkali-hydrolyzed nitrogen, available potassium and organic matter increased. At the same time, the total number of soil radiobacterium decreased and the total number of bacteria and fungi increased. Moreover, the activities of soil invertase, catalase, phosphatase and urease increased, while the invertase activity decreased. Compared with newly reclaimed soil and the first season soil, the pH, total nitrogen, and organic matter of continuous cropping soil decreased significantly with alkali-hydrolyzed nitrogen decreasing and the available phosphorus, total phosphorus, and available potassium increased significantly. In addition, the total number of soil radiobacterium and bacteria decreased in continuous cropping soil, while the total number of fungi increased and the ratio of total number of fungi to total number of bacteria increased significantly. Moreover, the activities of catalase, invertase, and sucrose increased, however the activities of phosphatase and urease decreased in continuous cropping soil.