Panax notoginseng (Burk) F. H. Chen, called Sanqi, is a valuable herbal plant and is widely used in Chinese medicine. However, the yield and saponin content cannot be guaranteed due to irrational irrigation and fertilizer management in low-latitude regions in southwestern China. To obtain suitable irrigation and organic fertilizer modes for improving the yield and saponin content of the plant, a shelter experiment was conducted using a randomized complete block design with a factorial arrangement of treatments with three replications. Three irrigation regimes, DL, DM and DS (irrigation upper/lower limit: 65–50% θf, 50–35% θf, and 35–20% θf, respectively, where θf is the field capacity), three organic fertilizer levels, FL, FM and FH (33, 48 and 63 t ha−1, respectively), and a control group, CK (65–50% θf and 3 t ha−1), were applied in the two-year and eight-month growth cycles. With the paired comparison design, the results indicated that the flower dry yield, root dry yield and Panax notoginseng saponins (PNS) were significantly affected by different water deficit irrigation and organic fertilizer treatments, and they first increased and then decreased with increased water deficit or organic fertilizer. Compared with DLFH, DMFM reduced water use by 42.39% and fertilizer use by 23.81%, and the flower dry yield, root dry yield, PNS, water use efficiency and partial factor productivity of fertilizer increased by 19.67%, 22.52%, 54.33%, 149.72% and 91.83%, respectively. Under the DMFM treatment, the dry root yield and saponin content for 3-year-old P. notoginseng were 3039.19 kg ha−1 and 10.85%, respectively, which were higher than those resulting from other treatments. Additionally, the PNS resulting from DMFM exhibited the highest comprehensive score and comprehensive index based on principal component analysis and the TOPSIS model. This combination could create a higher yield of flowers and roots, provide a scientific management for planting, and improve the economic benefits for planters and the local government.