Three smart spectrophotometric methods were developed for the simultaneous estimation of chlorpheniramine maleate and naphazoline hydrochloride, a binary mixture with overlapping spectra, without preliminary separation. These methods include area under the curve (AUC), graphical absorbance ratio (Q-analysis) and isosbestic point spectrophotometry. A comparative study among the methods was done showing the advantages and the disadvantages of each method. Beer’s law is obeyed over the concentration range of 5- 35 and 5-40 μg/ml for chlorpheniramine maleate and naphazoline hydrochloride,respectively (for area under the curve), and 5-40 μg/ml for each drug (for Q-analysis and isosbestic point). All the proposed methods were extensively validated according to the ICH guidelines and the obtained accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. The proposed methods were found to be rapid, simple and required no preliminary separation steps.