A new liquid chromatography methodology coupled to a diode array detector and a time-of-flight mass spectrometer has been developed for the simultaneous determination of phenolic compounds and saponins in quinoa (Chenopodium quinoa Willd). This method has allowed the simultaneous determination of these two families of compounds with the same analytical method for the first time. A fused-core column C18 has been used, and the analysis has been performed in less than 27 min. Both chromatographic and electrospray ionization time-of-flight mass spectrometry parameters have been optimized to improve the sensitivity and to maximize the number of compounds detected. A validation of the method has also been carried out, and free and bound polar fractions of quinoa have been studied. Twenty-five compounds have been tentatively identified and quantified in the free polar fraction, while five compounds have been tentatively identified and quantified in the bound polar fraction. It is important to highlight that 1-O-galloyl-β-D-glucoside, acacetin, protocatechuic acid 4-O-glucoside, penstebioside, ethyl-m-digallate, (epi)-gallocatechin, and canthoside have been tentatively identified for the first time in quinoa. Free phenolic compounds have been found to be in the range of 2.746-3.803 g/kg of quinoa, while bound phenolic compounds were present in a concentration that varies from 0.139 and 0.164 g/kg. Indeed, saponins have been found to be in a concentration that ranged from 5.6 to 7.5% of the total composition of whole quinoa flour.