A novel and simple ultra-performance LC method was developed for the estimation of nadifloxacin (NAD), terbinafine hydrochloride (TBH), mometasone furoate (MMF), methyl paraben (MP), and propyl paraben (PP) in a topical pharmaceutical dosage formulation. The analysis was carried out on a Waters Acquity UPLC ethylene bridged hybrid C18 column (50 × 2.1 mm, 1.7 μm) with a flow rate of 0.4 mL/min in gradient mode at a wavelength of 255 nm. Elution of all components was achieved within 9 min. The retention times of MP, NAD, PP, TBH, and MMF were observed at 1.5, 2.6, 3.4, 6.0, and 6.9 min, respectively. The proposed method was validated per current International Conference on Harmonization guidelines for specificity, precision, linearity, accuracy, range, LOD, LOQ, robustness, filter paper interference, and solution stability parameters. A complete method study was performed to determine the stability-indicating nature of the developed method.