Efficient nutrient management is essential for mitigating nutrient losses from farmland in the Erhai Lake Basin (ELB). This 2-year field study (2021-2022) in the northern ELB investigated the effects of different fertilizer application methods on nitrogen and phosphorus losses. The four fertilizer treatments included: no fertilizer, farmer practice of solely organic fertilizer application (FP), mineral fertilizer, and a combination of organic and mineral fertilizers (OMC). Over the study period, total N (TN) losses ranged from 17 to 34 kgha-1 and total P (TP) losses from 1.0 to 1.4 kgha-1. Peak N and P losses occurred during June and July, with N lost primarily as nitrate and P lost primarily in dissolved forms. Compared with the FP treatment, the OMC treatment significantly reduced nutrient losses throughout the tobacco season; TN runoff decreased by 2.7 kgha-1, TP runoff by 0.1 kgha-1, TN leaching by 21% and TP leaching by 17%. Also, the OMC treatment increased the average tobacco yield by 3.8% (to 2.55 tha-1) compared to the FP treatment, which in turn enhanced the gross value. Fertilizer treatments significantly affected soil properties. These altered soil properties, particularly alkaline hydrolysis N and soil organic matter levels, subsequently regulated N and P loss dynamics. These results provide a scientific basis for mitigating nutrient loss from farmland in the ELB through optimized fertilizer application.