The present study aimed to develop instant mushroom soup fortified with mixed Jerusalem artichoke and Cauliflower powders (JACF) instead of wheat flour at different levels (5, 10, 15, and 20%) based on dry weight as natural sources of protein, ash, fiber, inulin, and bioactive components. Based on the proximate analysis, adding JACF with 20% recorded the highest contents of protein, ash, fibers, and inulin as 24.73, 3.67, 9.67, and 9.17%, respectively. In the same line, macro- and microelements and essential amino acids showed a significant increase during fortification with 5–20% JACF compared to the control. In contrast, the total carbohydrate content and caloric values were decreased with the raised JACF concentration in the soup. The highest content of total phenolic acids, flavonoids, glucosinolates, carotenoids, and ascorbic acid was detected in mushroom soup with a 20% JACF mixture, which coincides with the highest antioxidant activity. Gallic (20.81–94.34 mg/100 g DW) and protocatechuic (13.63–58.53 mg/100 g) acids predominated among the phenolic acids identified in the mushroom-JACF soup samples, while rutin was the main flavonoid (7.52–18.2 mg/100 g). The increase of the JACF mixture in the soup significantly enhanced the rehydration ratio, total soluble solids, color parameters, and the sensory properties of the samples. In conclusion, using JACF in mushroom soup is necessary to improve the physicochemical characteristics and nutritional impact by containing phytochemicals and enhancing the organoleptic properties of the food product.