Two new, simple, fast and sensitive spectrophotometric methods were developed for analysis of binary mixtures of Lisinopril (LIS) and hydrochlorothiazide (HCT). These methods were absorptivity factor method and ratio subtraction method. In the first method, calculations were made using the absorbance of the mixtures at 211 nm where LIS absorptivity is half HCT absorptivity. On the other hand, the second method was based on obtaining the original spectrum of LIS from the zero order spectrum of the binary mixture then determining the concentration of LIS from its linear regression equation. HCT concentration in both methods was determined from the absorbance at 270 nm where a lack of interference of LIS occurs. The methods were validated according to ICH and applied successfully on different ratios of laboratory mixtures and on pharmaceutical tablets with excellent accuracy and precision.