The method has been proposed for the spectrophotometric determination of antibiotics of the cephalosporin (cefuroxime, ceftriaxone, cefotaxime, cefazolin) and penicillin (amoxicillin) groups using chemometric data processing (method of partial least squares, PLS). The absorption spectra of 24 binary mixtures of “cephalosporin – cephalosporin” and 16 binary mixtures of “cephalosporin – amoxicillin” with various concentrations in the range of 3–27 and 5–140 μg/ml have been recorded.