In this work, we aimed to develop and validate a new absorption factor spectrophotometric method for the assay of the paracetamol (PRA) and orphenadrine (ORP) combination in bulk and tablet dosage form. The method utilizes mathematical processing of the total absorbance of the PRA-ORP mixture at two precisely selected wavelengths (203 and 243 nm). Employing the established absorption factor of standard PRA at these wavelengths, the individual absorbance of each drug within the mixture is obtained, eliminating the need for prior separation. The method showed excellent linearity for both drugs within the concentration range of 2–14 μg/mL, and the correlation coefficients (R²) were 0.9985 and 0.9986 for PRA and ORP, respectively. The limit of detection (LOD) values were determined to be 0.14 μg/mL for PRA and 0.16 μg/mL for ORP. Similarly, the limit of quantification (LOQ) values were 0.44 and 0.48 μg/mL for PRA and ORP, respectively. Furthermore, the method exhibited high accuracy, with recoveries ranging from 99% to 102%, and excellent precision, demonstrated by relative standard deviation (%RSD) values below 2%. These findings confirm the validity of our developed method for the routine analysis of PRA and ORP in both bulk and tablet dosage forms, making it a practical and cost-effective approach for quality control purposes.