We created a simple, accurate, and precise reverse-phase high-performance liquid chromatography (RP-HPLC) method for estimating paracetamol, guaifenesin, and phenylephrine hydrochloride at the same time in a combined dosage form. An Inertsil ODS-3V C18 column (250 × 4.6 mm, 5 µm) was used to separate the samples. A gradient mobile phase of phosphate buffer (pH 3.0) and acetonitrile was used. The flow rate was 1.0 mL/min, and the detection was done at 220 nm. Paracetamol, guaifenesin, and phenylephrine HCl had retention times of about 3.84, 8.99, and 5.85 minutes, respectively. The method was linear for paracetamol, guaifenesin, and phenylephrine HCl in the ranges of 51.2–76.8 µg/mL, 32–60 µg/mL, and 16–24 µg/mL, with correlation coefficients (r) of 0.999 or higher for all analytes. The three drugs had average recoveries between 98.3% and 101.6%. The proposed method was validated in line with ICH guidelines and effectively utilized on a synthetic mixture of the analytes.