Using organic manures appears to be a promising strategy to promote plant performance and improve soil health in arid and semi-arid regions under the threat of changing climate. The objective of the current field-based study was to investigate the beneficial effects of cow dung manure (CDM) fermented at different days, including 7, 14, and 21 days, on cotton crop growth and soil health compared with synthetic fertilization. It was noticed that chemical fertilizer application showed the lowest values for cotton seedling growth, physio-biochemical attributes, and soil organic matter content. Results regarding CDM also showed that under all applied treatments, treatment in which 21 days of fermented manure was applied performed better in terms of cotton plant growth and soil properties, as evidenced by the cotton plant’s higher biomass, chlorophyll, and water contents, activities of antioxidant enzymes, lower soil pH, increased organic matter contents, and higher amounts of moisture and essential plant nutrient retention in soil. In summary, our study suggests that using CDM could be an efficient practice to improve the growth and development of crop plants and soil health.