Two chemometric methods were applied to the simultaneous determination of chlortetracycline (CTC) and benzocaine (BC) in their binary mixture. The methods involve multivariate calibration based on principal least-squares (PCR) and partial least-squares (PLS) regressions. A concentration set consisting of binary mixtures of CTC and BC in 13 different combinations were randomly prepared in 0,011 M HCl. Both multivariate calibration models were constructed by using the relationship between the concentration set and its corresponding absorption data in the spectral region of 200-305 nm, The accuracy and the precision of the methods were validated by analyzing synthetic mixtures containing investigated drugs. The recovery results obtained by applying PCR and PLS calibrations to artificial mixtures were found between 100.2 and 101.0%. Data treatments, regressions and statistical analysis were performed by using the Microsoft EXCEL and PLS toolbox 3.5 in Matlab 7.0 software. Satisfactory results for both artificial and commercial veterinary samples were obtained. The experimental results from two chemometric methods were compared with each other.