A new stability-indicating reversed-phase HPLC (RP-HPLC) method has been developed and validated for simultaneous assay of betamethasone dipropionate (BD) and chlorocresol and also for the estimation of BD related compounds in a pharmaceutical cream matrix. In addition, this newly developed RP-HPLC method was also demonstrated as suitable for a pharmaceutical ointment product that does not contain chlorocresol. The RP-HPLC method uses a Waters SymmetryShield RP18 analytical column (150 × 4.6 mm). Water (mobile phase A) and acetonitrile (mobile phase B) were used in the gradient elution with a flow rate of 1.5 mL/min and detection wavelength at 240 nm. A Waters XBridge Shield RP18 analytical column (150 × 4.6 mm) was identified as an alternate column. The limit of detection (LOD) and the limit of quantitation (LOQ) are 0.02 μg/mL and 0.05 μg/mL, respectively. The precision of the method for BD is less than 0.3% RSD, and the accuracy of BD ranged from 99.5% to 102.6%. The stability-indicating capability of this method has been demonstrated by analyzing aged samples of the product. This RP-HPLC method was successfully validated per ICH guidelines and proved to be suitable for routine quality control use.