The n-methylol dimethyl phosphono propionamide (MDPA) flame retardant compounds are predominantly used for cotton fabric treatments with trimethylol melamine (TMM) to obtain better crosslinking and enhanced flame retardant properties. Nevertheless, such treatments are associated with a toxic issue of cancer-causing formaldehyde release. An eco-friendly finishing was used to get formaldehyde-free fixation of flame retardant to the cotton fabric. Citric acid as a crosslinking agent along with the sodium hypophosphite as a catalyst in the treatment was utilized. The process parameters of the treatment were enhanced for optimized flame retardant properties, in addition, low mechanical loss to the fabric by response surface methodology using Box–Behnken statistical design experiment methodology was achieved. The effects of concentrations on the fabric’s properties (flame retardancy and mechanical properties) were evaluated. The regression equations for the prediction of concentrations and mechanical properties of the fabric were also obtained for the eco-friendly treatment. The R-squared values of all the responses were above 0.95 for the reagents used, indicating the degree of relationship between the predicted values by the Box–Behnken design and the actual experimental results. It was also found that the concentration parameters (crosslinking reagents and catalysts) in the treatment formulation have a prime role in the overall performance of flame retardant cotton fabrics.