For quality evaluation purposes, a simple, cost-effective, precise, accurate, and rapid planar chromatographic method was developed and validated for the separation of sulfadoxine, sulfalene, and pyrimethamine using standard thin-layer chromatographic plates and a mobile phase consisting of a mixture of toluene, ethyl acetate, and methanol in the ratio 50:28.5:21.5 (% v/v). Densitometric evaluation was carried out by scanning the plates at a wavelength of λ = 254 nm. The method was validated with respect to specificity, linearity, precision, and accuracy. Linearity was proven in a concentration range of 1.00–3.00 μg per spot for sulfalene/sulfadoxine and 0.050–0.150 μg per spot for pyrimethamine with linear regression coefficients (R2) of 0.980–0.990 for all substances. The values for limit of detection (LOD) were 0.107 ng per spot for sulfadoxine, 0.044 ng per spot for sulfalene, and 1.623 ng per spot for pyrimethamine, whereas those for limit of quantification (LOQ) were found to be 0.324 ng per spot for sulfadoxine, 0.133 ng per spot for sulfalene, and 4.92 ng per spot for pyrimethamine.