In this study, a two-year field experiment was conducted in a typical wax gourd growing area in South China, in which six treatments were set up: conventional fertilizer (CK), fertilizer reduction (Mg0), and additional application of 30, 60, 90, 120 kg/hm²MgO (Mg1, Mg2, Mg3, Mg4) on the basis of Mg0. By measuring the differences of soil Mg, nitrogen (N), phosphorus (P), potassium (K) and calcium (Ca) leaching in different treatments during the planting period of wax gourd, evaluating soil Mg nutrient balance, and analyzing the effects of different soil and environmental factors on soil Mg leaching loss, the effects of different nutrient management measures on soil Mg leaching loss and identify the key factors that increase soil Mg leaching loss were explored. The results showed that the cumulative leaching amounts of Mg, N, P, K and Ca under Mg0 were reduced by 36.19%–40.50%, 29.68%–36.86%, 21.14%–46.74%,39.65–42.83% and 29.65%–48.60% compared with CK, respectively. After the application of Mg fertilizer, the cumulative leaching amounts of Mg was increased by 42.46%–78.79%, 53.94%–69.92%, 78.92%–101.83% and 133.07%–134.37% in Mg1, Mg2, Mg3 and Mg4 compared with Mg0, and the exchangeable Mg content was increased by 69.02%–81.10% and 68.70%–78.54% in Mg3 and Mg4 compared with Mg0. In addition, soil cation exchange capacity (CEC) of Mg3 and Mg4 increased by 9.44%–34.93% and 14.26%–38.31% compared with Mg0, respectively. The contents of soil exchangeable Mg, rainfall, soil CEC, exchangeable Ca and available K significantly affected the leaching of soil Mg. In conclusion, in soil Mg nutrition management in wax gourd growing area of South China, attention should be paid to the application of slow Mg fertilizer and the balanced application of other fertilizers to reduce the leaching loss of Mg.