The aim of the present study is to develop stability-indicating reverse phase-high performance liquid chromatography-photo diode array (RP-HPLC-PDA) method for the simultaneous estimation of terbutaline sulphate and doxofylline in the presence of their degradation products. The method uses a Phenomenex C 18 reverse phase column (250 mm × 4.6 mm, 5 µm) with mobile phase consisting 15 mM ammonium acetate-methanol (70:30 v/v) at isocratic mode with an injection volume of 20 µL, and the eluents were monitored at 220 nm. Both drugs were subjected to the hydrolysis (acidic, basic), oxidation, and photolytic and thermal stress conditions. Considerable degradation of the both drugs was observed in basic hydrolysis and in oxidation stress conditions. The retention times of terbutaline sulphate and doxofylline were 4.1 and 13.3 min, respectively, and showed a good linearity in the concentration range of 1 to 5 µg/mL for terbutaline sulphate and 40 to 200 µg/mL for doxofylline with a correlation coefficient > 0.999 for both drugs. The validation parameters like specificity, system suitability, linearity, detection, quantification limits, precision, and robustness were all within the limits as per International Conference on Harmonisation (ICH) guidelines. The proposed RP-HPLC-PDA method is specific, accurate, and liquid chromatography-mass spectroscopy (LC-MS) compatible and was successfully applied for the simultaneous estimation of terbutaline sulphate and doxofylline in bulk and in tablet dosage forms.