As an alternative to chemicals, the use of phytohormones and growth regulators is considered as a novel method of enhancing the yield, quality parameters and nutritional capacity of fruit crops. Physiological responses and changes in quality attributes, yield, and phytochemicals of pomegranate fruits in response to foliar spray with different concentrations of methyl jasmonate (MeJA) at different growth and development stages were studied. MeJA in a concentration dependent manner, from 0.1 to 0.5 mM, substantially increased fruit total antioxidant and phenylalanine ammonialyase activities, total phenolics, ellagic acid, punicalagin, and tannic acid contents, sweetness, total soluble solids, whole fruit, aril and peel weights, firmness and juice content at harvest. MeJA substantially decreased fruit respiration rate and titratable acidity. Compared to the control, fruits from the trees treated with 0.5 mM MeJA showed 133% increase in aril weight, 141.4% increase in peel weight, 101% increase in fruit weight, and 24.7% increase in juice content (p ≤ 0.01). As a novel finding, the results showed that multiple spray of pomegranate trees and fruits with 0.5 mM MeJA is as an effective and practical strategy to enhance the yield, quality, and phytochemical contents of pomegranates.