Freshwater shortage and inadequate nutrient management are the two major challenges for sustainable wheat production in arid agro-ecosystems. Relatively little is known about the positive roles of the application methods for the combination of salicylic acid (SA) and plant nutrients in sustaining wheat production under arid climatic conditions. A two-year field study was undertaken to assess the impact of seven treatments for the integrated application of SA, macronutrients, and micronutrients on the morpho-physiological traits, yield, and irrigation water use efficiency (IWUE) of wheat subjected to full (FL) and limited (LM) irrigation regimes. The results showed that the LM regime caused a significant reduction in different plant growth traits, relative water content, chlorophyll pigments, yield components, and yield, while a significant increase was observed in IWUE. The sole application of SA or co-application with micronutrients through soil did not significantly affect the studied traits under the FL regime, while they achieved some improvement over untreated plants under the LM regime. Based on the different multivariate analyses, the soil and foliar applications for the combinations of SA and micronutrients, as well as a foliar application for the combinations of SA, macronutrients, and micronutrients were identified as an efficient option for mitigating the negative impacts of water deficit stress and enhancing the growth and production of wheat under normal conditions. In conclusion, the results obtained herein indicated that the co-application of SA and macro- and micronutrients is an effective option to greatly enhance and improve the growth and production of wheat crops in water-scarce countries of arid regions, such as Saudi Arabia, while an appropriate application method for this combination was required for positive effects.