The yield of Panax notoginseng (BurK.) F. H. Chen in Yunnan Province accounted for more than 90% of China's total yield, but extensive water and fertilizer management restricted improvement of yield, quality, and economic benefits of Panax notoginseng. Therefore, this study tried to propose an adaptive irrigation and fertilizer management strategy for Panax notoginseng production. A two-year (2017 and 2018) rain-shelter cultivation study in Yunnan Province of southwest China was conducted to analyze the influences of irrigation and organic fertilizer application on soil water distribution, root growth, water-fertilizer productivity, quality, and economic benefits of Panax notoginseng in four organic fertilizer application rates [500 (F1), 1000 (F2), 1500 (F3), and 2000 (F4) kg ha−1] combined with three micro-sprinkler irrigation schedules [I1: moderate deficit micro-sprinkler irrigation, (70–75%) θFC; I2: alternate micro-sprinkler irrigation, (70–75%) θFC / (80–85%) θFC; I3: slight deficit micro-sprinkler irrigation, (80–85%) θFC]. The results indicated that the increasing micro-sprinkler irrigation levels enhanced soil water content in 0–40 cm soil layer, but resulted in a reduction irrigation water productivity (IWP). Moreover, the increasing organic fertilizer application significantly led to reduced partial fertilizer productivity (PFP). Under the interaction of micro-sprinkler irrigation schedules and organic fertilizer application in 2017 and 2018, the I2F3 significantly obtained the highest soil water storage (SWS), root hydraulic conductivity, root morphological characteristics, root-shoot ratio, lowest root rot rate (4.68% in 2017 and 6.59% in 2018), largest yield (3614.5 kg ha−1 in 2017 and 3981.5 kg ha−1 in 2018), total saponin content (20.23% in 2017 and 23.28% in 2018), and economic benefits (25.28 × 104 $ ha−1 in 2017 and 32.6 × 104 $ ha−1 in 2018) of Panax notoginseng. Based on the above results, the comprehensive evaluation of five saponin contents and the comprehensive evaluation of the yield, IWP, PFP, economic benefits, and total saponin content of Panax notoginseng were analyzed by using a TOPSIS model in 2017 and 2018. We found that synergistic of alternate micro-sprinkler irrigation [I2, (70–75%) θFC / (80–85%) θFC] and organic fertilizer application (F3, 1500 kg ha−1) could decrease root rot, improve root growth, water-fertilizer productivity, quality, and economic benefits of Panax notoginseng.