This study presents the development and validation of a stability-indicating UPLC method for the simultaneous estimation of Sulfamethoxazole and Clindamycin in both bulk and formulated forms. The method was validated following ICH Q2(R1) guidelines, assessing parameters such as accuracy, precision, and ruggedness. Forced degradation studies were conducted under various stress conditions, including acidic, basic, oxidative, wet heat, and UV exposure, to evaluate the stability of the drugs. The method demonstrated high accuracy with recovery rates between 99.62% and 100%, and precision with %RSD values below 0.23%. Significant degradation was observed under acidic and basic conditions, while the drugs remained stable under oxidative and wet heat conditions. The developed method effectively distinguishes the active pharmaceutical ingredients from their degradation products, confirming its suitability for routine quality control and stability testing.