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This study presents optimization of dyeing variables for dyeing 100% cotton fabric with two novel bifunctional reactive dyes D-1 and D-2. These dyes have sulfatovinylsulfone and monochlorotriazine functional moieties. The impact of different variables, including dyeing temperature, salt concentration, and alkali, was investigated and optimized using response surface methodology (RSM). In spite of an exploring structural difference between both of these dyes, the dyeing temperature was optimized at the same value (61.68°C). The optimized conditions of salt (43.33 g/L) and alkali (29.50 g/L) for D-1 were resulted in 72.29% (±3) of exhaustion and 67.45% (±3) fixation. Similarly, D-2 showed 69% (±3) of exhaustion and 62.5% (±3) fixation at optimum value of salt (44.05 g/L) and alkali (33.87 g/L) concentration. Results showed better fixation and exhaustion of D-1 than dye D-2 which may be attributed to its more structural planarity and lower steric hindrance. The different fastness behaviors of dyes were found good to excellent for both dyes. The results attained were useful and suitable for commercial dyeing processes.