Water scarcity, especially in arid areas, has encouraged efforts to replace water sources for food production and agricultural development. Wastewater is one of the most accessible water resources with high potential for use in agriculture. The aim of this study was to investigate the effect of irrigation methods and water quality on morphological and physiological indices and leaf nutrient content of Osage orange seedlings in Yazd province in central Iran as an arid zone. Experimental treatments as a factorial experiment in a randomized complete block included quality of irrigation, water clean water (CW), raw wastewater (RW), and treated wastewater (TW), and irrigation method, surface irrigation (SI), and subsurface leaky irrigation (SLI). Statistical testing revealed that compared with the SI system, the SLI system increased leaf area (27%), height (13%), trunk diameter (8%), root length (9%), root fresh (30%) and dry weight (31%), and canopy fresh (25%) and dry weight (31%). Plots irrigated with RW had more SPAD, electrolyte leakage (EL), and water use efficiency (WUE; 29% 3%, and 67% respectively) than plots irrigated with CW. The highest levels of WUE (1.35 kgm3) were recorded when seedlings were grown using the SLI system and received RW. The results suggest that water quality was more effective than irrigation system for the uptake of elements in the leaves and the vegetative growth of Maclura pomifera, as RW showed the highest values of plant growth indices.