This study assessed the performance of Pleurotus ostreatus and Lentinula edodes mushrooms on a variety of substrate combinations. Water hyacinth, rice husk, and cow dung were employed as substrates. Mushroom growth performance, yield, proximate composition, and mineral content were among the variables evaluated. The results indicate significant differences (p < 0.05) in spawn run duration, first harvest duration, total yield, and biological efficiency among the substrate combinations for the mushroom species. The substrate combination of 80% water hyacinth and 20% cow dung consistently exceeded the performances of others, demonstrating higher total yield (863.00 and 799.81 g/bag) and biological efficiency (88.51% and 82.03%) for P. ostreatus and L. edodes mushrooms, respectively. Proximate analysis results also demonstrated that this substrate combination produced mushrooms with higher protein (14.72 and 12.04%) and carbohydrate (55.11 and 58.05%) contents for P. ostreatus and L. edodes, respectively. P, K, Mg, Na, Ca, Fe, Zn, and Cd levels in P. ostreatus samples ranged from 1700 to 2700, 28100 to 39500, 1600 to 7800, 291.55 to 400.23, 310.37 to 372.70, 26.42 to 45.47, 61.87 to 70.40, and 1.13–1.25 mg/kg on average, respectively. The levels for P, K, Mg, Na, Ca, Fe, Zn, and Cd ranged from 19700 to 22700, 22500 to 25000, 2100 to 2500, 250.96 to 300.90, 284.66 to 296.19, 24.04 to 29.49, 74.03 to 83.98, and 1.31–1.45 mg/kg for L. edodes samples. The evaluated mushrooms grown on the various substrate combinations contain higher major and minor minerals needed in the human diet than toxic elements. This indicated that the evaluated edible mushrooms had high important mineral levels and could be considered a good source of vital elements. They are also very good at balancing nutrient supply scarcity, which is common in developing countries like Ethiopia. However, according to the World Health Organization's permissible limits for human intake, adequate attention and control of daily dietary intake is necessary for specific elements.