Although Apocynum venetum L. is a valuable native species in China for economic and industrial purposes, less studies have been conducted to determine the optimum fertilizer application rate for cultivating it. The leaves of A. venetum are used as traditional Chinese herbs and the fiber is referred to as “king of wild fiber’’ because of its anti-microbial and anti-UV features. It grows in poor soils but currently populations of wild A. venetum in China are decreasing rapidly. Developing cultivation techniques for endangered A. venetum to achieve sustainable long-term use of this plant resource has become urgent and important. The role of nutrient supply in increasing yield and quality is currently unknown. To maximize the productivity and economic value of A. venetum, a 3-yr nutrient trial was conducted under drip irrigation to evaluate optimal fertilizer application for producing high yield (dry leaves) and better quality. The effects of N/P combination (N0-0 kg/ha, N1-17.4 kg/ha, N2-34.8 kg/ha, and N3-52.2 kg/ha; P0-0 kg/ha, P1-28.6 kg/ha, P2-57.2 kg/ha, and P3-85.8 kg/ha) on plant growth, yield, as well as the quality of drip-fertilized A. venetum, in northwest China were also investigated. Principal component analysis (PCA) and membership function analysis were implemented to develop a comprehensive evaluation model of nutrient interactions to determine the best N/P fertilizer application scheme for simultaneous yield and quality improvement of A. venetum. Overall, fertilization promoted the growth of A. venetum. With increasing fertilizer application, the growth, leaf yield, and quality of A. venetum tended to increase and then decrease. The maximum leaf yield was achieved under T6 (N2P2) treatment that was increased by 213.1 %, 184.3 %, and 88.3 % compared with controls from 2018 to 2020, respectively. Under T6 as well, the best total flavonoid, rutin, and isoquercitrin contents were observed, which were increased by 52.17 %, 68.39 %, and 128.07 % on average for three years. Correlation analysis showed that agronomic traits (plant height, stem diameter, secondary branch, and reproductive branch number) were positively correlated with both yield (aboveground biomass, yield) and quality (rutin, isoquercitrin, and total flavonoids content). According to the comprehensive evaluation model, the optimum N/P fertilizer pairing combination was N2P2, which resulted in the best quality and highest yield of A. venetum. The current research determined the fertilizer application to cultivate A. venetum and elucidated the effects on productivity and quality. This study provides a foundation for developing cultivation practices of A. venetum and promoting its application.