Wheat, being a major cereal crop, is negatively influenced by drought. The use of vermicompost may help wheat to tolerate the negative effects of drought stress. The present study investigated the effects of cellulolytic microbesenriched wheat straw vermicompost on morphological, physiological, and biochemical attributes of wheat under different soil moisture regimes. The treatments included three factors, viz, (a) three soil moisture levels (D0 = 70% field capacity (no drought), D1 =45% field capacity (moderate drought), and D2 =30% field capacity (severe drought)), and (b) four levels of cellulolytic microbe-enriched vermicompost prepared from wheat straw (VT0 = control, VT1 =4 t ha(-1), VT2 =6 t ha(-1), VT3 =8 t ha(-1)) and (c) two different wheat cultivars Galaxy-13 (drought-sensitive) and Faisalabad-08 (drought tolerant). Data on various morphological, physiological, enzymatic antioxidants, and biochemical parameters were recorded. Results indicated that morpho-physiological growth of wheat was negatively affected by moisture deficit conditions; however, the application of vermi-fertilizer increased the growth performance of wheat, particularly under drought. Under severe drought, VT2 treatment increased the root and shoot biomass (fresh/dry) by 19.04-44.82%, photosynthetic rate by 36.67-59.20%, photosynthetic pigments by 16.90-26.19%, relative water contents by 8.82-9.72%, antioxidant enzymes (catalase, superoxide dismutase, peroxidase) by 17.81-43.35%, leaf nutrient (nitrogen, phosphorus, potassium) accumulation by 17.64-47.39% in both wheat cultivars over control. In short, the application of cellulolytic microbe-enriched wheat straw vermicompost particularly VT2 was effective in alleviating the adverse impacts of drought stress on wheat.